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Crosstalk between steroid receptors and the c-Src-receptor tyrosine kinase pathways: implications for cell proliferation

Abstract

Both steroids and growth factors stimulate proliferation of steroid-dependent tumor cells, and interaction between these signaling pathways may occur at several levels. Steroid receptors are typically classified as ligand-activated transcription factors, and steps by which they bind ligand, dimerize, recruit coregulatory molecules, and activate target gene transcription are well understood. Several steroid responses are functionally linked to c-Src or tyrosine kinase receptors, and the physiological impact and the precise molecular pathways involved in these responses are under intensive investigation. Ligand-independent stimulation of steroid receptor-mediated transcription by growth factors is now believed to occur through activated protein kinases that phosphorylate the receptors and receptor coregulators. Recently, steroid hormones themselves have been shown to rapidly activate intracellular signaling cascades, via binding to cognate cytoplasmic or membrane-associated receptors. In some contexts, steroid receptors interact directly with c-Src and other cytoplasmic signaling molecules, such as Shc, PI3K, and p130 Cas. Crosstalk between growth factors and steroids in both the cytoplasm and nucleus could have profound impact on complex biological processes such as cell growth, and play a significant role in the treatment of steroid-dependent cancers. The potential roles of progesterone and estrogen receptors in this crosstalk are discussed in this review.

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References

  • Adesanya OO, Zhou J, Samathanam C, Powell-Braxton L and Bondy CA . (1999). Proc. Natl. Acad. Sci. USA, 96l, 3287–3291.

  • Ahola TM, Manninen T, Alkio N and Ylikoma T . (2002). Endocrinology, 143, 3376–3384.

  • Ankrapp DP, Bennett JM and Haslam SZ . (1998). J. Cell Physiol., 174, 251–260.

  • Arnold H and Notides AC . (1995). Mol. Endocrinol., 9, 24–33.

  • Ballare C, Uhrig M, Bechtold T, Sancho E, Di Domenico M, Migliaccio A, Auricchio F and Beato M . (2003). Mol. Cell. Biol., 23, 1994–2008.

  • Bamberger AM, Bamberger CM, Gellersen B and Schulte HM . (1996). Proc. Natl. Acad. Sci. USA, 93, 6169–6174.

  • Barletta F, Wong C-W, McNally C, Lomm BS, Katzenellenbogen BS and Cheskis BJ . (2004). Mol. Endocrinol., 18, 1096–1108.

  • Beato M . (1989). Cell, 56, 335–344.

  • Biscardi JS, Maa MC, Tice DA, Cox ME, Leu TH and Parsons SJ . (1999). J. Biol. Chem., 274, 8335–8343.

  • Biscardi JS, Ishizawar RC, Silva CM and Parsons SJ . (2000). Breast Cancer Res., 2, 203–210.

  • Bjornstrom L, Kilic E, Norman M, Parker MG and Sjoberg M . (2001). J. Mol. Endocrinol., 27, 93–106.

  • Bjornstrom L and Sjoberg M . (2002). Mol. Endocrinol., 16, 2202–2214.

  • Boonyaratanakornkit V, Scott MP, Ribon V, Sherman L, Anderson SM, Maller JL, Miller WT and Edwards DP . (2001). Mol. Cell, 8, 269–280.

  • Brinkman A, Van der Flier S, Lok EM and Dorssers LC . (2000). J. Natl. Cancer Inst., 92, 112–120.

  • Bunone G, Briand PA, Miksicek RJ and Picard D . (1996). EMBO J., 15, 2174–2183.

  • Cabodi S, Moror L, Baj G, Smeriflio M, di Stefano P, Gippone S, Surico N, Silengo L, Turco E, Tarone G and Defilippi P . (2004). J. Cell Sci., 117, 1603–1611.

  • Castoria G, Barone MV and Di Domenico M . (1999). EMBO J., 18, 2500–2510.

  • Castoria G, Migliaccio A, Bilancio A, Di Domenico M, de Falco A, Lombardi M, Fiorentino R, Varricchio L, Barone MV and Auricchio F . (2001). EMBO J., 20, 6050–6059.

  • Chen H, Lin RJ, Xie W, Wilpitz D and Evans RM . (1999). Cell, 98, 675–684.

  • Cho H and Katzenellenbogen BS . (1993). Mol. Endocrinol., 7, 441–452.

  • Clarke R, Leonessa F, Welch JN and Skaar TC . (2001). Pharmacol. Rev., 53, 25–71.

  • Clark DE, Poteet-Smith CE, Smith JA and Lannigan DA . (2001). EMBO J., 20, 3484–3494.

  • Couse JF and Korach KS . (1999). Endocr. Rev., 20, 358–417.

  • Curtis SW, Wahsburn T, Sewlall G, DiAugustine R, Lindzay J, Couse JF and Korach KS . (1996). Proc. Natl. Acad. Sci. USA, 93, 12626–12630.

  • Dickson RB, Huff KK, Spencer EM and Lippman ME . (1986). Endocrinology, 118, 138–142.

  • Dutertre M and Smith CL . (2003). Mol. Endocrinol., 17, 1296–1314.

  • Edwards DP, Weigel NL, Nordeen SK and Beck CA . (1993). Breast Cancer Res. Treat., 27, 41–56.

  • Faulds MH, Olsen H, Helguero LA, Gustafsson J-Ã… and Haldosén L-A . (2004). Mol. Endocrinol., 18, 412–421.

  • Faulds MH, Pettersson K, Gustafsson J-Ã… and Haldosen LA . (2001). Mol. Endocrinol., 15, 1929–1940.

  • Filardo EJ, Quinn JA, Bland KI and Frackelton Jr AR . (2000). Mol. Endocrinol., 14, 1649–1660.

  • Foley E, Jazaeri O, Shupnik MA, Jazaeri AA and Rice LW . (2000). Cancer Res., 60, 245–248.

  • Font de Mora J and Brown M . (2000). Mol. Cell. Biol., 20, 5041–5047.

  • Frasor J, Stossi F, Danes JM, Komm B, Lyttle CR and Katzenellenbogen BS . (2004). Cancer Res., 64, 1522–1533.

  • Fuqua SAW, Schiff R, Parra I, Moore JT, Mohsin SK, Osborne CK, Clark GM and Allred DC . (2003). Cancer Res., 63, 2434–2439.

  • Gothard LQ, Hibbard JC and Seyfred MA . (1996). Mol. Endocrinol., 10, 185–195.

  • Gu Q, Korach KS and Moss RL . (1999). Endocrinology, 140, 660–666.

  • Hom YK, Young P, Weisen JF, Mietten PJ, Derynck R, Werb Z and Cunha GR . (1998). Endocrinology, 139, 913–921.

  • Ignar-Trowbridge DM, Nelson KG, Bidwell MC, Curtis SW, Washburn TF, McLachlan JA and Korach KS . (1992). Proc. Natl. Acad. Sci. USA, 89, 4658–4662.

  • Ignar-Trowbridge DM, Teng CT, Ross KA, Parker MG, Korach KS and McLachlan JA . (1993). Mol. Endocrinol., 7, 992–998.

  • Jazaeri AA, Nunes KJ, Dalton MS, Shupnik MA and Rice LW . (2001). Oncogene, 20, 6965–6969.

  • Jeng M-H, Shupnik MA, Bender TP, Bandyopadhyay D, Westin EH, Kumar R, Masamura S and Santen RJ . (1998). Endocrinology, 139, 4167–4174.

  • Joel PB, Smith J, Sturgill TW, Fisher TL, Blenis J and Lannigan DA . (1998). Mol. Cell Biol., 18, 1978–1984.

  • Jordan VC, Wolf MF, Mirecki DM, Whitford DA and Welshons WV . (1988). Crit. Rev. Clin. Lab. Sci., 26, 97–152.

  • Kahlert S, Neudling S, van Eickels M, Vetter H, Meyer R and Grohe C . (2000). J. Biol. Chem., 275, 33551–33556.

  • Kato S, Endoh H, Masuhiro Y, Kitamoto T, Uchiyama S, Sasaki H, Masushige S, Gotoh Y, Nishida E, Kawashima H, Metzger D and Chambon P . (1995). Science, 270, 1491–1494.

  • Kerkhoff E, Houben R, Loffler S, Troppmair J, Lee JE and Rap UR . (1998). Oncogene, 16, 211–216.

  • Kloth MT, Laughlin KK, Biscardi JS, Boerner JL, Parsons SJ and Silva CM . (2003). J. Biol. Chem., 278, 1671–1679.

  • Klotz DM, Hewitt SC, Korach KS and DiAugustine RP . (2000). Endocrinology, 141, 3430–3439.

  • Klotz DM, Hewitt SC, Ciana P, Raviscioni M, Lindzey JK, Foley J, Maggi A, DiAugustine RP and Korach KS . (2002). J. Biol. Chem., 277, 8531–8537.

  • Knowlden JM, Hurtchenson IA, Jones HE, Madden T, Gee JMW, Harper ME, Barrow D, Wakeling AE and Nicholson RI . (2003). Endocrinology, 144, 1032–1044.

  • Kousteni S, Bellido T, Plotkin LI, O'Brien CA, Bodenner DL, Han L, Han K, DiGregorio GB, Katzenellenbogen JA, Katzenellenbogen BS, Roberson PK, Weinstein RS, Jilka RL and Manolagas SC . (2001). Cell, 104, 719–730.

  • Kuiper GG, Carlsson B, Grandien K, Enmark E, Haffblad J, Nilsson S and Gustafsson JA . (1997). Endocrinology, 138, 863–870.

  • Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S and Gustafsson J-A . (1996). Proc. Natl. Acad. Sci. USA, 93, 5925–5930.

  • Kumar R, Wang RA, Mazumdar A, Talukder AH, Mandal M, Yang Z, Bagheri-Yarmand R, Sahin A, Hortobagyi G, Adam L, Barnes CJ and Vadlamudi RK . (2002). Nature, 418, 654–657.

  • Kushner PJ, Agard DA, Greene GL, Scanlan TS, Shiau AK, Uht RM and Webb P . (2000). J. Steroid Biochem. Mol. Biol., 74, 311–317.

  • Labriola L, Salatino M, Proietti CJ, Pecci A, Soco OA, Kornblihtt AR, Charreau EH and Elizalde PV . (2003). Mol. Cell. Biol., 23, 1095–1111.

  • Lange C . (2004). Mol. Endocrinol., 18, 269–278.

  • Lange CA, Richer JK and Horwitz KB . (1999). Mol. Endocrinol., 13, 829–836.

  • Lange CA, Richer JK, Shen T and Horwitz KB . (1998). J. Biol. Chem., 273, 31308–31318.

  • Lange CA, Shen T and Horwitz KB . (2000). Proc. Natl. Acad. Sci. USA, 97, 1032–1037.

  • Lannigan DA . (2003). Steroids, 68, 1–9.

  • Levin ER . (2003). Mol. Endocrinol., 17, 309–317.

  • Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M and Chambon P . (1995). Cell, 83, 835–839.

  • Martin MB, Franke TF, Stoica GE, Chambon P, Katzenellenbogen BS, Stoica BA, McLemore MS, Olivo SE and Stoica A . (2000). Endocrinology, 141, 4503–4511.

  • Marsaud V, Gougelet A, Maillard S and Renoir J-M . (2003). Mol. Endocrinol., 17, 2013–2027.

  • Metivier R, Penot G, Hubner MR, Reid G, Brand H, Kos M and Gannon F . (2003). Cell, 115, 751–763.

  • McClelland RA, Barrow D, Madden T, Dutkowski CM, Pamment J, Knolden J, Gee JM and Nicholson RI . (2001). Endocrinology, 142, 2776–2788.

  • Migliaccio A, Castoria G, Di Domenico M, de Falco A, Bilancio A, Lombardi M, Barone MV, Ametrano D, Zannini MS, Abbondanza C and Auricchio F . (2000). EMBO J., 19, 5406–5417.

  • Migliaccio A, Di Domenico M, Castoria G, De Faclo A, Bontempo P, Nola E and Auricchio F . (1996). EMBO J., 15, 1292–1300.

  • Migliaccio M, Piccolo D, Cqastoria G, Di Domenico M, Bilancio A, Lombardi M, Gong W, Beato M and Auricchio F . (1998). EMBO J., 17, 2008–2018.

  • Moe-Behrens GHG, Klinger FG, Eskild W, Grotmol T, Haugen TB and De Felici M . (2003). Mol. Endocrinol., 17, 2630–2638.

  • Nawaz Z and O'Malley BW . (2004). Mol. Endocrinol., 18, 493–499.

  • Nicholson RI, McClelland RA, Robertson JFR and Gee JMW . (1999). Endocr. Relat. Cancer, 6, 373–387.

  • Norris JD, Fan D, Kerner SA and McDonnell DP . (1997). Mol. Endocrinol., 11, 747–754.

  • Paech K, Webb P, Kuiper GG, Nilsson S, Gustafsson J, Kushner PJ and Scanlan TS . (1997). Science, 277, 1508–1510.

  • Paruthiyil S, Parmar H, Kerekatte V, Cunha GR, Firestone GL and Leitman DC . (2004). Cancer Res., 64, 423–428.

  • Pearce ST and Jordan VC . (2004). Crit. Rev. Oncol. Hematol., 50, 3–22.

  • Petz LN and Nardulli AM . (2000). Mol. Endocrinol., 14, 972–985.

  • Petz LN, Ziegler YS, Loven MA and Nardulli AM . (2002). Endocrinology, 143, 4583–4591.

  • Qiu M, Olsen A, Faivre E, Horwitz KB and Lange CA . (2003). Mol. Endocrinol., 17, 628–642.

  • Qiu M and Lange CA . (2003). J. Steroid Biochem. Mol. Biol., 85, 147–157.

  • Razandi M, Alton G, Pderam A, Ghonshani S, Webb P and Levin ER . (2003a). Mol. Cell. Biol., 23, 1633–1646.

  • Razandi M, Oh P, Poedram A, Schnitzer J and Levin ER . (2002). Mol. Endocrinol., 16, 100–115.

  • Razandi M, Pedran A, Greene GL and Levin ER . (1999). Mol. Endocrinol., 13, 307–319.

  • Razandi M, Pedram A, Park ST and Levin ER . (2003b). J. Biol. Chem., 278, 2701–2712.

  • Reid G, Hubner MR, Metivier R, Brand H, Denger S, Manu D, Beaudouin J, Ellenberg J and Gannon F . (2003). Mol. Cell, 11, 695–707.

  • Richards RG, DiAugustine RP, Petrusz P, Clark GC and Sebastian J . (1996). Proc. Natl. Acad. Sci. USA, 93, 12002–12007.

  • Richer JK, Lange CA, Manning NG, Owen G, Powell R and Horwitz KB . (1998). J. Biol. Chem., 273, 31317–33132.

  • Ricketts DL, Ryall G, Bakhshi R, Rawson NS, Gazet J, Nolan C and Coombes RC . (1991). Cancer Res., 51, 1817–1822.

  • Riggins RB, Quilliam LA and Bouton AH . (2003). J. Biol. Chem., 278, 28264–28273.

  • Salh B, Marotta A, Matthewson C, Ahluwalia M, Flint J, Owen D and Pelech S . (1999). Anticancer Res., 19, 731–740.

  • Sartorius CA, Melville MY, Hovland AR, Tung L, Takimoto GS and Horwitz KB . (1994). Mol. Endocrinol., 8, 1347–1360.

  • Saville B, Wormke M, Wang F, Nguyen T, Enmark E, Kuiper G, Gustafsson JA and Safe S . (2000). J. Biol. Chem., 275, 5379–5387.

  • Schlegel A, Wang C, Katzenellenbogen BS, Pestell RG and Lisanti MP . (1999). J. Biol. Chem., 274, 33551–33556.

  • Segars JH and Driggers PH . (2002). Trends Endocrinol. Metab., 13, 349–354.

  • Shang Y, Hu X, DiRenzo J, Lazar MA and Brown M . (2000). Cell, 103, 843–852.

  • Shen T, Horwitz KB and Lange CA . (2001). Mol. Cell. Biol., 21, 6122–6131.

  • Shiau AK, Barstad D, Loria PM, Cheng L, Kushner PJ, Agard DA and Greene GL . (1998). Cell, 95, 927–937.

  • Shim W-S, Conaway M, Masamura S, Yue W, Wang J-P, Kumar R and Santen RJ . (2000). Endocrinology, 141, 396–405.

  • Simoncini T, Hafezi-Moghadam A, Brazil DP, Ley K, Chin WW and Liao JK . (2000). Nature, 407, 538–541.

  • Singleton DW, Feng Y, Burd CJ and Khan SA . (2003). Endocrinology, 144, 121–128.

  • Song RX, Barnes CJ, Zhang ZG, Bao YD, Kumar R and Santen RJ . (2004). Proc. Natl. Acad. Sci. USA, 101, 2076–2081.

  • Song RX-D, McPherson RA, Adam L, Bao Y, Shupnik M, Kumar R and Santen RJ . (2002). Mol. Endocrinol., 6, 116–127.

  • Sotiriou C, Neo SY, McShane LM, Korn EL, Long PM, Jazaeri A, Martiat P, Fox SB, Harris AL and Liu ET . (2003). Proc. Natl. Acad. Sci. USA, 100, 10393–10398.

  • Stoica GE, Franke TF, Wellstein A, Czubayko F, List H-J, Reiter R, Morgan E, Martin MB and Stoica A . (2003). Mol. Endocrinol., 17, 818–830.

  • Stoner M, Wormke M, Saville B, Samudio I, Qin CH, Abdelrahim M and Safe S . (2004). Oncogene, 23, 1052–1063.

  • Strawn Jr EY, Novy MJ, Burry KA and Bethea CL . (1995). Am. J. Obstet. Gynecol., 172, 1837–1843.

  • Strom A, Hartman JS, Foster S, Kietz S, Wimalesena J and Gustafsson J-A . (2004). Proc. Natl. Acad. Sci. USA, 101, 1566–1571.

  • Sun M, Paciga JE, Feldman RI, Yuan Z, Coppola D, Lu YY, Shelley SA, Nicosia SV and Cheng JQ . (2001). Cancer Res., 61, 5985–5991.

  • Sutherland RL, Prall OWJ, Watts CKW and Musgrove EA . (1998). J. Mammary Gland Biol. Neoplasia, 3, 63–72.

  • Tice DA, Biscardi JS, Nickles AL and Parsons SJ . (1999). Proc. Natl. Acad. Sci. USA, 96, 1415–1420.

  • Toran-Allerand CD . (2004). Endocrinology, 145, 1069–1074.

  • Tremblay A, Tremblay GB, Labrie F and Giguere V . (1999). Mol. Cell, 3, 513–519.

  • Tremblay GB, Tremblay A, Copeland NG, Gilbert DJ, Jenkins NA, Labrie F and Giguère V . (1997). Mol. Endocrinol., 11, 353–365.

  • Tsai H-W, Katzenellenbogen JA, Katzenellenbogen BS and Shupnik MA . (2004). Endocrinology, 145, 2730–2738.

  • van der Flier S, Chan CM, Brinkman A, Smid M, Johnston SR, Dorssers LC and Dowsett M . (2000). Int. J. Cancer, 89, 465–468.

  • van der Flier S, van der Kwast TH, Claassen CJ, Timmermans M, Brinkman A, Henzen-Logmans SC, Foekens JA and Dorssers LC . (2001). Int. J. Biol. Markers, 16, 172–178.

  • Watson CS, Norfleet AM, Pappas TC and Gametchu B . (1999). Steroids, 64, 5–13.

  • Weber JD, Raben DM, Phillips PJ and Baldassare JJ . (1997). Biochem. J., 326, 61–68.

  • Weigel NL and Zhang Y . (1999). J. Mol. Med., 76, 469–479.

  • Westin S, Rosenfeld MG and Glass CK . (2000). Adv. Pharmacol., 47, 89–112.

  • Wong CW, McNally C, Nickbarg E, Komm BS and Cheskis BJ . (2002). Proc. Natl. Acad. Sci. USA, 192, 5696–5699.

  • Yamashita H, Iwase H, Toyama T and Fujii Y . (2003). Oncogene, 22, 1638–1652.

  • Yue W, Wang J-P, Conaway M, Masamura S, Li Y and Santen RJ . (2002). Endocrinology, 143, 3221–3229.

  • Zhu Y, Bond J and Thomas P . (2003). Proc. Natl. Acad. Sci. USA, 100, 2237–2242.

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Shupnik, M. Crosstalk between steroid receptors and the c-Src-receptor tyrosine kinase pathways: implications for cell proliferation. Oncogene 23, 7979–7989 (2004). https://doi.org/10.1038/sj.onc.1208076

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