Somatostatin and Epidermal Growth Factor Receptors: Implications in Breast Cancer

Ujendra Kumar, Geetanjali Kharmate


Despite several advances, the underlying mechanism of complexity of breast cancer progression still remains elusive. In addition to the genetic predisposition, several growth factor receptors including insulin growth factor receptor (IGF), platelet derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) relaying proliferative signals are accountable for disease progression. Epidermal growth factor receptors (EGFRs, or commonly known as ErbBs), members of the receptor tyrosine kinase family (RTKs), play a central role in tumor growth, progression and metastatic disease. Typically, agonist dependent activation of EGFR results in receptor phosphorylation, homo- and/or heterodimerization and modulation of signaling pathways leading to cell proliferation, survival and metastasis. Targeting one or multiple steps in EGFR-mediated tumor progression may serve as a better approach in drug therapies. Unlike EGFRs, G-protein coupled somatostatin receptors (SSTRs) have been recognized as negative regulators of breast tumors. The activation of SSTRs modulates downstream signaling responsible for tumor growth and consequent cytostatic or cytotoxic effects on tumor proliferation. SSTR subtypes are well characterized to form homo-and/or heterodimers within the same family as well as with other GPCRs. Clinically, the chimeric molecule targeting both SSTR5 and dopamine receptors (specifically dopamine receptor 2) is in use for the treatment of pituitary tumors. This review describes the interplay between SSTRs and EGFR and the potential role of such cross talk in attenuation of EGFR-mediated signaling pathways involved in tumorigenesis. Furthermore, recent findings supporting the role of SSTR in EGFR-mediated signaling in tumor biology are discussed in detail.


Breast Cancer, Dimerization, Heterodimerization, Epidermal growth factor, Epidermal growth factor Receptors, Somatostatin, Somatostatin Receptors


Abd El-Rehim DM, Pinder SE, Paish CE, Bell JA, Rampaul RS, Blamey RW, Robertson JF, Nicholson RI & Ellis IO 2004 Expression and co-expression of the members of the epidermal growth factor receptor (EGFR) family in invasive breast carcinoma. Br J Cancer 91 1532-1542

Albérini JL, Meunier B, Denzler B, Devillers A, Tass P, Dazord L, Simple TL, Laissue J, Jong Rd, Cloirec JL, Reubi JC & Bourguet P 2000 Somatostatin receptor in breast cancer and axillary nodes: study with scintigraphy, histopathology and receptor autoradiography. Breast Cancer Res Treat 61 21-32

Alroy I & Yarden Y 1997 The ErbB signaling network in embryogenesis and oncogenesis: signal diversification through combinatorial ligand-receptor interactions. FEBS Lett 410 83-86

Alvarez RH, Valero V & Hortobagyi GN 2010 Emerging Targeted Therapies for Breast Cancer. Journal of Clinical Oncology 28 3366-3379

Bajaj M, Waterfield MD, Schlessinger J, Taylor WR & Blundell T 1987 On the tertiary structure of the extracellular domains of the epidermal growth factor and insulin receptors. Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology 916 220-226.

Baragli A, Alturaihi H, Watt HL, Abdallah A, & Kumar U. 2007 Heterooligomerization of human dopamine receptor 2 and somatostatin receptor 2: Co-immunoprecipitation and fluorescence resonance energy transfer analysis. Cell Signal 19 2304-2316

Baselga J, Albanell J, Ruiz A, Lluch A, Gascon P, Guillem V, Gonzalez S, Sauleda S, Marimon I, Tabernero JM, Koehler MT & Rojo F 2005 Phase II and tumor pharmacodynamic study of gefitinib in patients with advanced breast cancer. J Clin Oncol 23 5323-5333

Ben-Shlomo A & Melmed S 2008 Somatostatin agonists for treatment of acromegaly. Mol Cell Endocrinol 286 192-198

Bo AH, Hou JC, Lan YH, Tian YT & Zhang JY 2008 Over-expression of EGFR in breast cancer. Chinese Journal of Cancer Research 20 69-72

Bose P & Ozer H 2009 Neratinib: an oral, irreversible dual EGFR/HER2 inhibitor for breast and non-small cell lung cancer. Expert Opinion on Investigational Drugs 18 1735-1751

Bouchalova K, Cizkova M, Cwiertka K, Trojanec R, Friedecky D & Hajduch M 2010 Lapatinib in breast cancer - the predictive significance of HER1 (EGFR), HER2, PTEN and PIK3CA genes and lapatinib plasma level assessment. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 154 281-288

Bousquet C, Guillermet J, Vernejoul F, Lahlou H, Buscail L & Susini C 2004 Somatostatin receptors and regulation of cell proliferation. Dig Liver Dis 36 Suppl 1 S2-7

Bozionellou V, Mavroudis D, Perraki M, Papadopoulos S, Apostolaki S, Stathopoulos E, Stathopoulou A, Lianidou E & Georgoulias V 2004 Trastuzumab administration can effectively target chemotherapy-resistant cytokeratin-19 messenger RNA-positive tumor cells in the peripheral blood and bone marrow of patients with breast cancer. Clin Cancer Res 10 8185 - 8194

Bruno JF, Xu Y, Song J & Berelowitz M 1992 Molecular Cloning and Functional Expression of a Brain-Specific Somatostatin Receptor. Proc. Nat. Acad Sci 89 11151-11155

Buscail L, Esteve J, Saint-Laurent N, Bertrand V, Reisine T, O'Carroll A, Bell GI, Schally AV, Vaysse N & Susini C 1995 Inhibition of Cell Proliferation by the Somatostatin Analogue RC-160 is Mediated by Somatostatin Receptor Subtypes SSTR2 and SSTR5 Through Different Mechanisms. Proc Nat Acad Sci 92 1580-1584

Buscail L, Vernejoul F, Faure P, Torrisani J and Susini C 2002 Regulation of cell proliferation by somatostatin. Ann Endocrinol (Paris) 63 2S13 - 12S18

Cameron Smith M, Orlando C, Serio M & Maggi M 2003 Somatostatin receptors and breast cancer. J Endocrinol Invest 26 125-130

Campos SM 2008 Anti-Epidermal Growth Factor Receptor Strategies for Advanced Breast Cancer. Cancer Investigation 26 757-768

Canobbio L, Cannata D, Miglietta L & Boccardo F 1995 Somatuline (BIM 23014) and tamoxifen treatment of postmenopausal breast cancer patients: clinical activity and effect on insulin-like growth factor-I (IGF-I) levels. Anticancer Res 15 2687-2690

Carpenter G, King L & Cohen S 1978 Epidermal growth factor stimulates phosphorylation in membrane preparations in vitro. Nature 276 409-410

Cervia D & Bagnoli P 2007 An update on somatostatin receptor signaling in native systems and new insights on their pathophysiology. Pharmacol Ther 116 322-341

Chaudhury AR, Gerecke KM, Wyss JM, Morgan DG, Gordon MN & Carroll SL 2003 Neuregulin-1 and erbB4 immunoreactivity is associated with neuritic plaques in Alzheimer disease brain and in a transgenic model of Alzheimer disease. J Neuropathol Exp Neurol 62 42-54

Chrysogelos SA & Dickson RB 1994 EGF receptor expression, regulation, and function in breast cancer. Breast Cancer Research and Treatment 29 29-40.

Ciardiello F & Tortora G 2001 A Novel Approach in the Treatment of Cancer: Targeting the Epidermal Growth Factor Receptor. Clinical Cancer Research 7 2958-2970

Citri A & Yarden Y 2006 EGF-ERBB signalling: towards the systems level. Nat Rev Mol Cell Biol 7 505-516

Courtney KD, Corcoran RB & Engelman JA 2010 The PI3K Pathway As Drug Target in Human Cancer. Journal of Clinical Oncology 28 1075-1083

Csaba Z & Dournaud P 2001 Cellular biology of somatostatin receptors. Neuropeptides 35 1-23

Darnell JE, Kerr IM & Stark GR 1994 Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 264 1415-1421

Daub H, Weiss FU, Wallasch C & Ullrich A 1996 Role of transactivation of the EGF receptor in signalling by G-protein-coupled receptors. Nature 379 557-560

de Weille JR, Schmid-Antomarchi H, Fosset M & Lazdunski M 1989 Regulation of ATP-sensitive K+ channels in insulinoma cells: activation by somatostatin and protein kinase C and the role of cAMP. Proc Natl Acad Sci U S A 86 2971-2975

Deming SL, Nass SJ, Dickson RB & Trock BJ 2000 C-myc amplification in breast cancer: a meta-analysis of its occurrence and prognostic relevance. Br J Cancer 83 1688-1695

DiGiovanna MP, Stern DF, Edgerton SM, Whalen SG, Moore D, 2nd & Thor AD 2005 Relationship of epidermal growth factor receptor expression to ErbB-2 signaling activity and prognosis in breast cancer patients. J Clin Oncol 23 1152-1160

Earp HS, Dawson TL, Li X & Yu H 1995 Heterodimerization and functional interaction between EGF receptor family members: a new signaling paradigm with implications for breast cancer research. Breast Cancer Research and Treatment 35 115-132

Easton DF, Ford D & Bishop DT 1995 Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Am J Hum Genet 56 265-271

Evans AA, Crook T, Laws SA, Gough AC, Royle GT & Primrose JN 1997 Analysis of somatostatin receptor subtype mRNA expression in human breast cancer. Br J Cancer 75 798-803

Florio T, Thellung S, Arena S, Corsaro A, Bajetto A, Schettini G & Stork PJ 2000 Somatostatin receptor 1 (SSTR1)-mediated inhibition of cell proliferation correlates with the activation of the MAP kinase cascade: role of the phosphotyrosine phosphatatse SHP-2. J Physiol Paris 94 239 - 250

Florio T, Yao H, Carey KD, Dillon TJ & Stork PJ 1999 Somatostatin activation of mitogen-activated protein kinase via somatostatin receptor 1 (SSTR1). Mol Endocrinol 13 24-37

Gadella TW & Jovin TM 1995 Oligomerization of epidermal growth factor receptors on A431 cells studied by time-resolved fluorescence imaging microscopy. A stereochemical model for tyrosine kinase receptor activation. The Journal of Cell Biology 129 1543-1558

Garrett TPJ, McKern NM, Lou M, Elleman TC, Adams TE, Lovrecz GO, Zhu H-J, Walker F, Frenkel MJ, Hoyne PA, Jorissen RN, Nice EC, Burgess AW & Ward CW 2002 Crystal Structure of a Truncated Epidermal Growth Factor Receptor Extracellular Domain Bound to Transforming Growth Factor α. Cell 110 763-773

Goldenberg MM 1999 Trastuzumab, a recombinant DNA-derived humanized monoclonal antibody, a novel agent for the treatment of metastatic breast cancer. Clin Ther 21 309-318

Gospodarowicz D 1981 Epidermal and nerve growth factors in mammalian development. Annu Rev Physiol 43 251-263

Grant M, Collier B & Kumar U 2004 Agonist-dependent Dissociation of Human Somatostatin Receptor 2 Dimers: A Role in Receptor Trafficking. J. Biol. Chem. 279 36179-36183

Grant M & Kumar U 2009 The role of G-proteins in the dimerisation of human somatostatin receptor types 2 and 5. Regul Pept 159 3-8

Grant M, Patel R & Kumar U 2004 The role of subtype-specific ligand binding and the C-tail domain in dimer formation of human somatostatin receptors. J Biol Chem 279 38636 - 38643

Gullick WJ 2001 The Type 1 growth factor receptors and their ligands considered as a complex system. Endocr Relat Cancer 8 75-82

Guy PM, Platko JV, Cantley LC, Cerione RA & Carraway KL, 3rd 1994 Insect cell-expressed p180erbB3 possesses an impaired tyrosine kinase activity. Proc Natl Acad Sci U S A 91 8132-8136

Hagemeister AL & Sheridan MA 2008 Somatostatin inhibits hepatic growth hormone receptor and insulin-like growth factor I mRNA expression by activating the ERK and PI3K signaling pathways. Am J Physiol Regul Integr Comp Physiol 295 R490-497

Hahn CG, Wang HY, Cho DS, Talbot K, Gur RE, Berrettini WH, Bakshi K, Kamins J, Borgmann-Winter KE, Siegel SJ, Gallop RJ & Arnold SE 2006 Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia. Nat Med 12 824-828

Harding J & Burtness B 2005 Cetuximab: an epidermal growth factor receptor chemeric human-murine monoclonal antibody. Drugs Today (Barc) 41 107-127

Harris RC, Chung E & Coffey RJ 2003 EGF receptor ligands. Experimental Cell Research 284 2-13

Heldin C-H 1995 Dimerization of cell surface receptors in signal transduction. Cell 80 213-223

Herbst RS 2004 Review of epidermal growth factor receptor biology. International Journal of Radiation Oncology*Biology*Physics 59 S21-S26

Herbst RS, Maddox AM, Rothenberg ML, Small EJ, Rubin EH, Baselga J, Rojo F, Hong WK, Swaisland H, Averbuch SD, Ochs J & LoRusso PM 2002 Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non-small-cell lung cancer and other solid tumors: results of a phase I trial. J Clin Oncol 20 3815-3825

Huang CM, Wu YT & Chen ST 2000 Targeting delivery of paclitaxel into tumor cells via somatostatin receptor endocytosis. Chemistry & Biology 7 453-461

Ikeda SR & Schofield GG 1989 Somatostatin blocks a calcium current in rat sympathetic ganglion neurones. J Physiol 409 221-240

Reubi JC 1990 Somatostatin receptor incidence and distribution in breast cancer using receptor autoradiography: Relationship to egf receptors. Intnl J Can 46 416-420

Jaquet P, Gunz G, Saveanu A, Dufour H, Taylor J, Dong J, Kim S, Moreau JP, Enjalbert A & Culler MD 2005 Efficacy of chimeric molecules directed towards multiple somatostatin and dopamine receptors on inhibition of GH and prolactin secretion from GH-secreting pituitary adenomas classified as partially responsive to somatostatin analog therapy. Eur J Endocrinol 153 135-141

Jordan BA, Trapaidze N, Gomes I, Nivarthi R & Devi LA 2001 Oligomerization of opioid receptors with beta 2-adrenergic receptors: a role in trafficking and mitogen-activated protein kinase activation. Proc Natl Acad Sci U S A 98 343-348

Jorissen RN, Walker F, Pouliot N, Garrett TPJ, Ward CW & Burgess AW 2003 Epidermal growth factor receptor: mechanisms of activation and signalling. Experimental Cell Research 284 31-53

Kallergi G, Agelaki S, Kalykaki A, Stournaras C, Mavroudis D & Georgoulias V 2008 Phosphorylated EGFR and PI3K/Akt signaling kinases are expressed in circulating tumor cells of breast cancer patients. Br Cancer Res 10 R80

Kallergi G, Agelaki S, Markomanolaki H, Georgoulias V & Stournaras C 2007a Activation of FAK/PI3K/Rac1 signaling controls actin reorganization and inhibits cell motility in human cancer cells. Cell Physiol Biochem 20 977 - 986

Kallergi G, Mavroudis D, Georgoulias V & Stournaras C 2007b Phosphorylation of FAK, PI-3K, and impaired actin organization in CK-positive micrometastatic breast cancer cells. Mol Med 13 79 - 88

Katz M, Amit I & Yarden Y 2007 Regulation of MAPKs by growth factors and receptor tyrosine kinases. Biochim Biophys Acta 1773 1161-1176

Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, Revil C & Jones A 2009 Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol 27 5529-5537

Kharmate G, Rajput PS, Watt HL, Somvanshi RK, Chaudhari N, Qiu X & Kumar U 2011a Dissociation of epidermal growth factor receptor and ErbB2 heterodimers in the presence of somatostatin receptor 5 modulate signaling pathways. Endocrinology 152 931-945

Kharmate G, Rajput PS, Watt HL, Somvanshi RK, Chaudhari N, Qiu X & Kumar U 2011b Role of somatostatin receptor 1 and 5 on epidermal growth factor receptor mediated signaling. Biochim Biophys Acta 1813 1172-1189

King LE, Jr., Gates RE, Stoscheck CM & Nanney LB 1990 Epidermal growth factor/transforming growth factor alpha receptors and psoriasis. J Invest Dermatol 95 10S-12S

Kleuss C, Hescheler J, Ewel C, Rosenthal W, Schultz G & Wittig B 1991 Assignment of G-protein subtypes to specific receptors inducing inhibition of calcium currents. Nature 353 43-48

Kluxen F, Bruns C & Lubbert H 1992 Expression Cloning of a Rat Brain Somatostatin Receptor cDNA. Proc Natl Acad Sci USA 89 4618-4622

Kraus MH, Popescu NC, Amsbaugh SC & King CR 1987 Overexpression of the EGF receptor-related proto-oncogene erbB-2 in human mammary tumor cell lines by different molecular mechanisms. Embo J 6 605-610

Kristjansdottir K & Dizon D 2010 HER-dimerization inhibitors: evaluating pertuzumab in women's cancers. Expert Opinion on Biological Therapy 10 243-250

Kumar U, Grigorakis SI, Watt HL, Sasi R, Snell L, Watson P & Chaudhari S 2005 Somatostatin receptors in primary human breast cancer: quantitative analysis of mRNA for subtypes 1–5 and correlation with receptor protein expression and tumor pathology. Breast Cancer Res Treat 92 175-186

Lahlou H, Guillermet J, Hortala M, Vernejoul F, Pyronnet S, Bousquet C & Susini C 2004 Molecular Signaling of Somatostatin Receptors. Ann NY Acad Sci 1014 121-131

Lamberts SW, Krenning EP & Reubi JC 1991 The role of somatostatin and its analogs in the diagnosis and treatment of tumors. Endocr Rev 12 450-482

Lemmon M, Bu Z, Ladbury J, Zhou M, Pinchasi D, Lax I, Engelman D & Schlessinger J 1997 Two EGF molecules contribute additively to stabilization of the EGF dimer. EMBO 16 281-294

Liang K, Lu Y, Li X, Zeng X, Glazer RI, Mills GB & Fan Z 2006 Differential roles of phosphoinositide-dependent protein kinase-1 and akt1 expression and phosphorylation in breast cancer cell resistance to Paclitaxel, Doxorubicin, and gemcitabine. Mol Pharmacol 70 1045 - 1052

Liebow C, Hierowski M & duSapin K 1986 Hormonal control of pancreatic cancer growth. Pancreas 1 44-48

Lo HW, Xia W, Wei Y, Ali-Seyed M, Huang SF & Hung MC 2005 Novel prognostic value of nuclear epidermal growth factor receptor in breast cancer. Cancer Res 65 338-348

Mandarino L, Stenner D, Blanchard W, Nissen S, Gerich J, Ling N, Brazeau P, Bohlen P, Esch F & Guillemin R 1981

Selective effects of somatostatin-14, -25 and -28 on in vitro insulin and glucagon secretion. Nature 291 76-77

Martin O & Philippe IB 2008 Prolonged EGFR Signaling by ERBB2-Mediated Sequestration at the Plasma Membrane. Traffic 9 147-155

Meyerhof W 1998 The elucidation of somatostatin receptor functions: a current view. Rev Physiol Biochem Pharmacol 133 55-108

Montero JC, Ocana A, Abad M, Ortiz-Ruiz MJ, Pandiella A & Esparis-Ogando A 2009 Expression of Erk5 in Early Stage Breast Cancer and Association with Disease Free Survival Identifies this Kinase as a Potential Therapeutic Target. PLoS ONE 4 e5565

Nakagawa K, Tamura T, Negoro S, Kudoh S, Yamamoto N, Takeda K, Swaisland H, Nakatani I, Hirose M, Dong RP & Fukuoka M 2003 Phase I pharmacokinetic trial of the selective oral epidermal growth factor receptor tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839) in Japanese patients with solid malignant tumors. Ann Oncol 14 922-930

Nicholson KM & Anderson NG 2002 The protein kinase B/Akt signalling pathway in human malignancy. Cellular Signalling 14 381-395

Nicholson RI, Gee JMW & Harper ME 2001 EGFR and cancer prognosis. European Journal of Cancer 37 9-15

Normanno N, Bianco C, De Luca A, Maiello MR & Salomon DS 2003 Target-based agents against ErbB receptors and their ligands: a novel approach to cancer treatment. Endocrine-Related Cancer 10 1-21

Normanno N, De Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR, Carotenuto A, De Feo G, Caponigro F & Salomon DS 2006 Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 366 2-16

O'Byrne KJ, Dobbs N, Propper DJ, Braybrooke JP, Koukourakis MI, Mitchell K, Woodhull J, Talbot DC, Schally AV & Harris AL 1999 Phase II study of RC-160 (vapreotide), an octapeptide analogue of somatostatin, in the treatment of metastatic breast cancer. Br J Cancer 79 1413-1418

O'Carroll AM, Lolait SJ, Konig M & Mahan LC 1992 Molecular cloning and expression of a pituitary somatostatin receptor with preferential affinity for somatostatin-28. Mol Pharmacol 42 939-946

Ogiso H, Ishitani R, Nureki O, Fukai S, Yamanaka M, Kim J-H, Saito K, Sakamoto A, Inoue M, Shirouzu M & Yokoyama S 2002 Crystal Structure of the Complex of Human Epidermal Growth Factor and Receptor Extracellular Domains. Cell 110 775-787

Olayioye MA, Beuvink I, Horsch K, Daly JM & Hynes NE 1999 ErbB Receptor-induced Activation of Stat Transcription Factors Is Mediated by Src Tyrosine Kinases. Journal of Biological Chemistry 274 17209-17218

Olayioye MA, Neve RM, Lane H & Hynes NE 2000 The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J 19 3159 - 3167

Patel RC, Kumar U, Lamb DC, Eid JS, Rocheville M, Grant M, Rani A, Hazlett T, Patel SC, Gratton E & Patel YC 2002 Ligand binding to somatostatin receptors induces receptor-specific oligomer formation in live cells. Proc Natl Acad Sci U S A 99 3294-3299

Patel YC 1998 Basic aspects of somatostatin receptors. Advances in Molecular and Cellular Endocrinology.

Patel YC 1999 Somatostatin and Its Receptor Family. Frontiers in Neuroendocrinology 20 157-198

Patel YC 1990 Somatostatin-receptor imaging for the detection of tumors. N Engl J Med 323 1274-1276

Patel YC, Greenwood MT, Warszynska A, Panetta R & Srikant CB 1994 All five cloned human somatostatin receptors (hSSTR1-5) are functionally coupled to adenylyl cyclase. Biochem Biophys Res Commun 198 605 - 612

Pfeiffer M, Koch T, Schroder H, Klutzny M, Kirscht S, Kreienkamp HJ, Hollt V & Schulz S 2001 Homo- and heterodimerization of somatostatin receptor subtypes: inactivation of sst3 receptor function by heterodimerization with sst2A. J Biol Chem 276 14027-14036

Pfeiffer M, Koch T, Schroder H, Laugsch M, Hollt V & Schulz S 2002 Heterodimerization of Somatostatin and Opioid Receptors Cross-modulates Phosphorylation, Internalization, and Desensitization. J. Biol. Chem. 277 19762-19772

Pierce KL, Premont RT & Lefkowitz RJ 2002 Seven-transmembrane receptors. Nat Rev Mol Cell Biol 3 639 - 650

Pilichowska M, Kimura N, Fujiwara H & Nagura H 1987 Immunohistochemical study of TGF-alpha, TGF-beta1, EGFR and IGF-1 expression in human breast carcinoma. Mod Pathol 10 969-975

Prevost G, Hosford D & Thomas F 1994 Receptors for somatostatin and somatostatin analogues in human breast tumors. Ann N Y Acad Sci 733 147-154

Pyronnet S, Bousquet C, Najib S, Azar R, Laklai H & Susini C 2008 Antitumor effects of somatostatin. Mol Cell Endocrinol 286 230-237

Quesnelle KM, Boehm AL & Grandis JR 2007 STAT-mediated EGFR signaling in cancer. Journal of Cellular Biochemistry 102 311-319

Reisine T & Bell GI 1995 Molecular biology of somatostatin receptors. Endocr Rev 16 427-442

Reubi J-C, Waser B, Foekens J, Klijn J, Lamberts S & Laissue J 1990 Somatostatin receptor incidence and distribution in breast cancer using receptor autoradiography: relationship to EGF receptors. Int J Cancer 46 416-420

Rio C, Buxbaum JD, Peschon JJ & Corfas G 2000 Tumor necrosis factor-alpha-converting enzyme is required for cleavage of erbB4/HER4. J Biol Chem 275 10379-10387

Rivera JA, Alturaihi H & Kumar U 2005 Differential regulation of somatostatin receptors 1 and 2 mRNA and protein expression by tamoxifen and estradiol in breast cancer cells. J Carcinogen 4 10 - 19

Rocheville M, Lange DC, Kumar U, Patel SC, Patel RC & Patel YC 2000a Receptors for Dopamine and Somatostatin: Formation of Hetero-Oligomers with Enhanced Functional Activity. Science 288 154-157

Rocheville M, Lange DC, Kumar U, Sasi R, Patel RC & Patel YC 2000b Subtypes of the somatostatin receptor assemble as functional homo- and heterodimers. J Biol Chem 275 7862 - 7869

Rosen EM, Fan S, Pestell RG & Goldberg ID 2003 BRCA1 gene in breast cancer. J Cell Physiol 196 19-41

Savage CR, Jr., Inagami T & Cohen S 1972 The primary structure of epidermal growth factor. J Biol Chem 247 7612-7621

Saveanu A, Lavaque E, Gunz G, Barlier A, Kim S, Taylor JE, Culler MD, Enjalbert A & Jaquet P 2002 Demonstration of Enhanced Potency of a Chimeric Somatostatin-Dopamine Molecule, BIM-23A387, in Suppressing Growth Hormone and Prolactin Secretion from Human Pituitary Somatotroph Adenoma Cells. J Clin Endocrinol Metab 87 5545-5552

Schally AV 1988 Oncological applications of somatostatin analogues. Cancer Res 48 6977-6985

Schonbrunn A & Tashjian H, Jr 1978 Characterization of functional receptors for somatostatin in rat pituitary cells in culture. J Biol Chem 253 6473-6483

Setyono-Han B, Henkelman MS, Foekens JA & Klijn JGM 1987 Direct Inhibitory Effects of Somatostatin (Analogues) on the Growth of Human Breast Cancer Cells. Cancer Res 47 1566-1570

Sharma K, Patel YC & Srikant CB 1996 Subtype-selective induction of wild-type p53 & apoptosis, but not cell cycle arrest, by human somatostatin receptor 3. Mol Endocrinol 10 1688-1696

Sharma K & Srikant CB 1998 Induction of wild-type p53 Bax and acidic endonuclease during somatostatin signaled apoptosis in MCF-7 human breast cancer cells. Int J Cancer 76 259 - 266

Somvanshi RK, Billova S, Kharmate G, Rajput PS & Kumar U 2009 C-tail mediated modulation of somatostatin receptor type-4 homo- and heterodimerizations and signaling. Cell Signal 21 1396-1414

Somvanshi RK, War SA, Chaudhari N, Qiu X & Kumar U 2011 Receptor specific crosstalk and modulation of signaling upon heterodimerization between beta1-adrenergic receptor and somatostatin receptor-5. Cell Signal 23 794-811

Srikant CB & Patel YC 1981 Receptor binding of somatostatin-28 is tissue specific. Nature 294 259-260

Suo Z, Risberg B, Karlsson MG, Villman K, Skovlund E, & Nesland JM. 2002 The expression of EGFR family ligands in breast carcinomas. Int J Surg Pathol 10 91-99

Susini C & Buscail L 2006 Rationale for the use of somatostatin analogs as antitumor agents. Ann Oncol 17 1733-1742

Suzuki Y, Miura H, Tanemura A, Kobayashi K, Kondoh G, Sano S, Ozawa K, Inui S, Nakata A, Takagi T, Tohyama M, Yoshikawa K & Itami S 2002 Targeted disruption of LIG-1 gene results in psoriasiform epidermal hyperplasia. FEBS Lett 521 67-71

Thottassery JV, Sun Y, Westbrook L, Rentz SS, Manuvakhova M, Qu Z, Samuel S, Upshaw R, Cunningham A & Kern FG 2004 Prolonged extracellular signal-regulated kinase 1/2 activation during fibroblast growth factor 1- or heregulin beta1-induced antiestrogen-resistant growth of breast cancer cells is resistant to mitogen-activated protein/extracellular regulated kinase kinase inhibitors. Cancer Res 64 4637-4647

Toi M, Tominaga T, Osaki A & Toge T 1994 Role of epidermal growth factor receptor expression in primary breast cancer: results of a biochemical study and an immunocytochemical study. Breast Cancer Res Treat 29 51-58

Tran VT, Beal MF & Martin JB 1985 Two types of somatostatin receptors differentiated by cyclic somatostatin analogs. Science 228 492-495

Tsutsui S, Inoue H, Yasuda K, Suzuki K, Higashi H, Era S & Mori M 2005 Reduced expression of PTEN protein and its prognostic implications in invasive ductal carcinoma of the breast. Oncology 68 398-404

Ullrich A, Coussens L, Hayflick JS, Dull TJ, Gray A, Tam AW, Lee J, Yarden Y, Libermann TA, Schlessinger J, Downward J, Mayes ELV, Whittle N, Waterfield MD & Seeburg PH 1984 Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. Nature 309 418-425

Vikic-Topic S, Raisch KP, Kvols LK & Vuk-Pavlovic S 1995 Expression of somatostatin receptor subtypes in breast carcinoma, carcinoid tumor, and renal cell carcinoma. J Clin Endocrinol Metab 80 2974-2979

Vivanco I & Sawyers CL 2002 The phosphatidylinositol 3-Kinase-AKT pathway in human cancer. Nat Rev Cancer 2 489-501

Wang YN, Yamaguchi H, Hsu JM & Hung MC 2010 Nuclear trafficking of the epidermal growth factor receptor family membrane proteins. Oncogene 29 3997-4006

War SA, Somvanshi RK & Kumar U 2011 Somatostatin receptor-3 mediated intracellular signaling and apoptosis is regulated by its cytoplasmic terminal. Biochim Biophys Acta 1813 390-402

Watt H & Kumar U 2006 Colocalization of somatostatin receptors and epidermal growth factor receptors in breast cancer cells. Cancer Cell Intnl 6 5

Watt HL, Kharmate GD & Kumar U 2009 Somatostatin receptors 1 and 5 heterodimerize with epidermal growth factor receptor: agonist-dependent modulation of the downstream MAPK signalling pathway in breast cancer cells. Cell Signal 21 428-439

Weckbecker G, Tolcsvai L, Stolz B, Pollak M & Bruns C 1994 Somatostatin analogue octreotide enhances the antineoplastic effects of tamoxifen and ovariectomy on 7,12-dimethylbenz(alpha)anthracene-induced rat mammary carcinomas. Cancer Res 54 6334-6337

Weigel MT & Dowsett M 2010 Current and emerging biomarkers in breast cancer: prognosis and prediction. Endocr Relat Cancer 17 R245-262

Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C & Micklem G 1995 Identification of the breast cancer susceptibility gene BRCA2. Nature 378 789-792

Yamada Y, Kagimoto S, Kubota A, Yasuda K, Masuda K, Someya Y, Ihara Y, Li Q, Imura H, Seino S & Seino Y 1993 Cloning, Functional Expression and Pharmacological Characterization of a Fourth (hSSTR4) and a Fifth (hSSTR5) Human Somatostatin Receptor Subtype. Biochemical and Biophysical Research Communications 195 844-852

Yamada Y, Reisine T, Law SF, Ihara Y, Kubota A, Kagimoto S, Seino M, Seino Y, Bell GI & Seino S 1992 Somatostatin receptors, an expanding gene family: cloning and functional characterization of human SSTR3, a protein coupled to adenylyl cyclase. Mol Endocrinol 6 2136-2142

Yap TA, Garrett MD, Walton MI, Raynaud F, de Bono JS & Workman P 2008 Targeting the PI3K-AKT-mTOR pathway: progress, pitfalls, and promises. Current Opinion in Pharmacology 8 393-412

Yarden Y 2001 The EGFR family and its ligands in human cancer. signalling mechanisms and therapeutic opportunities. Eur J Cancer 37 Suppl 4 S3-8

Zhu Y & Yakel JL 1997 Calcineurin modulates G protein-mediated inhibition of N-type calcium channels in rat sympathetic neurons. J Neurophysiol 78 1161-1165

Zimmermann M, Zouhair A, Azria D & Ozsahin M 2006 The epidermal growth factor receptor (EGFR) in head and neck cancer: its role and treatment implications. Radiat Oncol 1 11

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