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Expression of estrogen receptor α, retinoic acid receptor α and cellular retinoic acid binding protein II genes is coordinately regulated in human breast cancer cells

Abstract

Human breast cancer cell lines expressing the estrogen receptor α (ERα), all-trans-retinoic acid (ATRA) receptor α (RARα) and cellular retinoic acid binding protein II (CRABPII) genes are sensitive to ATRA-mediated growth inhibition. To study the relationship among ERα, RARα and CRABPII expression, the protein levels of each member were compared in five breast cancer cell lines (T47D, MCF-7, ZR-75-1, Hs587 T and MDA-MB-231 cells) and two immortalized nontumorigenic breast epithelial cell lines (MTSV1.7 and MCF-10A). ERα, RARα and CRABPII proteins were detected in T47D, MCF-7 and ZR-75-1 cells but not in other tested cell lines. RARα and CRABPII proteins were either reduced or undetectable in T47D/C4:2W and MCF-7/ADR cells with lost expression of ERα. Estradiol increased and anti-estrogens (tamoxifen and ICI 164,384) downregulated the expression of both RARα and CRABPII proteins in T47D and MCF-7 cells. RARα antagonist Ro-41-5253 inhibited CRABPII expression, but not RARα expression in estradiol-treated T47D and MCF-7 cells. Suppression of ERα by small interfering RNA (siRNA) reduced RARα and CRABPII gene expression and siRNA suppression of RARα reduced CRABPII expression while having no effect on ERα in T47D cells. Transient transfection of either RARα or ERα expression vectors increased CRABPII expression in MDA-MB-231 cells but only RARα, not ERα, activated hCRABPII promoter reporter. These results indicate that there is a gene activation pathway in which ERα drives RARα transcription and RARα drives CRABPII transcription in ERα-positive human breast cancer cells.

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References

  • Anzano MA, Byers SW, Smith JM, Peer CW, Mullen LT, Brown CC, Roberts AB and Sporn MB . (1994). Cancer Res., 54, 4614–4617.

  • Apfel C, Bauer F, Crettaz M, Forni L, Kamber M, Kaufmann F, LeMotte P, Pirson W and Klaus M . (1992). Proc. Natl. Acad. Sci. USA, 89, 7129–7133.

  • Astrom A, Pettersson U and Voorhees JJ . (1992). J. Biol. Chem., 267, 25251–25255.

  • Astrom A, Tavakkol A, Pettersson U, Cromie M, Elder JT and Voorhees JJ . (1991). J. Biol. Chem., 266, 17662–17666.

  • Bartek J, Bartkova J, Kyprianou N, Lalani EN, Staskova Z, Shearer M, Chang S and Taylor-Papadimitriou J . (1991). Proc. Natl. Acad. Sci. USA, 88, 3520–3524.

  • Boylan JF, Lufkin T, Achkar CC, Taneja R, Chambon P and Gudas LJ . (1995). Mol. Cell. Biol., 15, 843–851.

  • Bucco RA, Zheng WL, Davis JT, Sierra-Rivera E, Osteen KG, Chaudhary AK and Ong DE . (1997). Biochemistry, 36, 4009–4014.

  • Busch C, Sakena P, Funa K, Nordlinder H and Eriksson U . (1990). Methods Enzymol., 189, 315–324.

  • Chambon P . (1996). FASEB J., 10, 940–954.

  • Dawson MI, Chao WR, Pine P, Jong L, Hobbs PD, Rudd CK, Quick TC, Niles RM, Zhang XK and Lombardo A . (1995). Cancer Res., 55, 4446–4451.

  • Degos L, Dombret H, Chomienne C, Daniel MT, Miclea JM, Chastang C, Castaigne S and Fenaux P . (1995). Blood, 85, 2643–2653.

  • Delva L, Bastie JN, Rochette-Egly C, Kraiba R, Balitrand N, Despouy G, Chambon P and Chomienne C . (1999). Mol. Cell. Biol., 19, 7158–7167.

  • Di W, Li XY, Datta S, Astrom A, Fisher GJ, Chambon P, Voorhees JJ and Xiao JH . (1998). J. Invest. Dermatol., 111, 1109–1115.

  • Fitzgerald P, Teng M, Chandraratna RA, Heyman RA and Allegretto EA . (1997). Cancer Res., 57, 2642–2650.

  • Fontana JA . (1987). Exp. Cell. Biol., 55, 136–144.

  • Gottardis MM, Bischoff ED, Shirley MA, Wagoner MA, Lamph WW and Heyman RA . (1996). Cancer Res., 56, 5566–5570.

  • Guo X, Ruiz A, Rando RR, Bok D and Gudas LJ . (2000). Carcinogenesis, 21, 1925–1933.

  • Han QX, Allegretto EA, Shao ZM, Kute TE, Ordonez J, Aisner SC, Rishi AK and Fontana JA . (1997). Diagn. Mol. Pathol., 6, 42–48.

  • Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, Gu LJ and Wang ZY . (1988). Blood, 72, 567–572.

  • Jiang SY, Langan-Fahey SM, Stella AL, McCague R and Jordan VC . (1992). Mol. Endocrinol., 6, 2167–2174.

  • Jing Y, Waxman S and Mira-y-Lopez R . (1997). Cancer Res., 57, 1668–1672.

  • Jing Y, Zhang J, Bleiweiss IJ, Waxman S, Zelent A and Mira YLR . (1996). FASEB J., 10, 1064–1070.

  • Li XH and Ong DE . (2003). J. Biol. Chem., 278, 35819–35825.

  • Lin X and Nelson WG . (2003). Cancer Res., 63, 498–504.

  • MacGregor TM, Copeland NG, Jenkins NA and Giguere V . (1992). J. Biol. Chem., 267, 7777–7783.

  • Mangelsdorf DJ, Umesono K and Evans RM . (1994). The Retinoid. Sporn MB, Roberts AB, Goodman DS (eds). Raven Press: New York, pp. 319–349.

  • Manor D, Shmidt EN, Budhu A, Flesken-Nikitin A, Zgola M, Page R, Nikitin AY and Noy N . (2003). Cancer Res., 63, 4426–4433.

  • Nakagawa S, Fujii T, Yokoyama G, Kazanietz MG, Yamana H and Shirouzu K . (2003). Mol. Carcinog., 38, 106–116.

  • Niles RM . (2000). Nutrition, 16, 1084–1089.

  • Noy N . (2000). Biochem. J., 348 Pt 3, 481–495.

  • Ong DE, Newcomer ME and Chytil F . (1994). The retinoids. Sporn, M. B., Roberts, A. B., Goodman, D. S. (eds). Raven Press: New York, pp. 283–317.

  • Pasquali D, Bellastella A, Valente A, Botti G, Capasso I, del Vecchio S, Salvatore M, Colantuoni V and Sinisi AA . (1997). Eur. J. Endocrinol., 137, 410–414.

  • Pink JJ, Bilimoria MM, Assikis J and Jordan VC . (1996). Br. J. Cancer, 74, 1227–1236.

  • Rishi AK, Shao ZM, Baumann RG, Li XS, Sheikh MS, Kimura S, Bashirelahi N and Fontana JA . (1995). Cancer Res., 55, 4999–5006.

  • Roman SD, Clarke CL, Hall RE, Alexander IE and Sutherland RL . (1992). Cancer Res., 52, 2236–2242.

  • Roman SD, Ormandy CJ, Manning DL, Blamey RW, Nicholson RI, Sutherland RL and Clarke CL . (1993). Cancer Res., 53, 5940–5945.

  • Rosenauer A, Nervi C, Davison K, Lamph WW, Mader S and Miller Jr WH . (1998). Cancer Res., 58, 5110–5116.

  • Ross AC and Ternus ME . (1993). J. Am. Diet. Assoc., 93, 1285–1290; quiz 1291–1292.

  • Rousseau C, Pettersson F, Couture MC, Paquin A, Galipeau J, Mader S and Miller Jr WH . (2003). J. Steroid Biochem Mol. Biol., 86, 1–14.

  • Schneider SM, Offterdinger M, Huber H and Grunt TW . (2000). Cancer Res., 60, 5479–5487.

  • Seewaldt VL, Johnson BS, Parker MB, Collins SJ and Swisshelm K . (1995). Cell Growth Differ., 6, 1077–1088.

  • Sheikh MS, Shao ZM, Chen JC, Hussain A, Jetten AM and Fontana JA . (1993). J. Cell. Biochem., 53, 394–404.

  • Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Woods WG, Ogden A, Weinstein H, Shepherd L, Willman C, Bloomfield CD, Rowe JM and Wiernik PH . (2002). Blood, 100, 4298–4302.

  • Tavakkol A, Griffiths CE, Keane KM, Palmer RD and Voorhees JJ . (1992). J. Invest Dermatol., 99, 146–150.

  • van der Burg B, van der Leede BM, Kwakkenbos-Isbrucker L, Salverda S, de Laat SW and van der Saag PT . (1993). Mol. Cell. Endocrinol., 91, 149–157.

  • van der Leede BJ, Folkers GE, van den Brink CE, van der Saag PT and van der Burg B . (1995). Mol. Cell. Endocrinol., 109, 77–86.

  • Van heusden J, Wouters W, Ramaekers FC, Krekels MD, Dillen L, Borgers M and Smets G . (1998). Br. J. Cancer., 77, 26–32.

  • Warrell Jr RP, Frankel SR, Miller Jr WH, Scheinberg DA, Itri LM, Hittelman WN, Vyas R, Andreeff M, Tafuri A and Jakubowski A . (1991). N. Engl. J. Med., 324, 1385–1393.

  • Widschwendter M, Berger J, Daxenbichler G, Muller-Holzner E, Widschwendter A, Mayr A, Marth C and Zeimet AG . (1997a). Cancer Res., 57, 4158–4161.

  • Widschwendter M, Daxenbichler G, Culig Z, Michel S, Zeimet AG, Mortl MG, Widschwendter A and Marth C . (1997b). Int. J. Cancer, 71, 497–504.

  • Widschwendter M, Daxenbichler G, Dapunt O and Marth C . (1995). Cancer Res., 55, 2135–2139.

  • Yang Q, Sakurai T and Kakudo K . (2002). Breast Cancer Res. Treat., 76, 167–173.

  • Zhao Z, Zhang ZP, Soprano DR and Soprano KJ . (1995). Exp. Cell Res., 219, 555–561.

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Acknowledgements

We thank the following investigators for sharing reagents: Joyce Taylor-Papadimitrou (MSTV1.7 cells), V Craig Jordan (T47D C4:2W and S30 cells), T-C Chou (MCF-7/Adr cells), Pierre Chambon (anti-RARα antibody, RARα, RXRα and ERα expression vectors) and John J Voorhees (human CRABPII promoter CAT reporter). This work was partly supported by American Institute for Cancer Research (YJ), NIH CA54273 (RML) and The Samuel Waxman Cancer Research Foundation.

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Lu, M., Mira-y-Lopez, R., Nakajo, S. et al. Expression of estrogen receptor α, retinoic acid receptor α and cellular retinoic acid binding protein II genes is coordinately regulated in human breast cancer cells. Oncogene 24, 4362–4369 (2005). https://doi.org/10.1038/sj.onc.1208661

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