Artículo
Lanari, C.; Giulianelli, S.; Vaqué, J.P.; Wargon, V.; Soldati, R.; Vanzulli, S.I.; Martins, R.; Zeitlin, E.; Helguero, L.; Lamb, C.; Molinolo, A.A.; Gutkind, J.S. "The role of estrogen receptor alpha in breast cancer cell proliferation mediated by progestins " (2012) Medicina (Argentina). 72(4):315-320
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Abstract:
In C4-HD murine mammary carcinomas and in human breast cancer T47D cells, we showed that medroxyprogesterone acetate (MPA) induces a nuclear physical association between estrogen receptor alpha (ERα) and progesterone receptors (PR). The blockade of ERα inhibits cell proliferation mediated by progestins. We hypothesized that this nuclear association between ERα/PR is necessary to trigger progestin-induced cell proliferation and tumor growth. We demonstrated that fulvestrant (FUL, ICI182.780) induced complete regression of C4-HD tumors growing with progestins. MPA treatment induced an early increase in both CCND1 and MYC expression in T47D cells. The blockade of ERα prevented the MPA-dependent transcription of both genes. Specific binding of PR/ERα was observed at the same MPA-sensitive regions at the CCND1 and MYC gene promoters after chromatin immunoprecipitation (ChIP) analysis. ICI inhibited binding of ERα to both gene regulatory sequences while PR binding was unaffected. The nuclear colocalization between both receptors in T47D cells was confirmed by: confocal microscopy, Duolink assays and co-immunoprecipitation assays. In breast cancer samples we also observed a nuclear interaction between both steroid receptors. Our results indicate that the presence of ERα interacting with activated PR at the CCND1 and MYC promoters is required to trigger progestin-induced gene transcription and cell proliferation in breast cancer cells.
Registro:
| Documento: | Artículo |
| Título: | The role of estrogen receptor alpha in breast cancer cell proliferation mediated by progestins |
| Autor: | Lanari, C.; Giulianelli, S.; Vaqué, J.P.; Wargon, V.; Soldati, R.; Vanzulli, S.I.; Martins, R.; Zeitlin, E.; Helguero, L.; Lamb, C.; Molinolo, A.A.; Gutkind, J.S. |
| Filiación: | Instituto de Biología y Medicina Experimental, IByME-CONICET, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina Oral and Pharyngeal Cancer Branch, NIDCR, NIH, Bethesda, United States Academia Nacional de Medicina, Argentina Policlínica Bancaria, Buenos Aires, Argentina Universidade de Aveiro, Aveiro, Portugal |
| Palabras clave: | Breast cancer; CCND1/MYC; ERα; MPA; PR; CCND1 protein; estrogen receptor alpha; fulvestrant; gestagen; medroxyprogesterone acetate; membrane protein; Myc protein; progesterone receptor; unclassified drug; animal cell; animal cell culture; article; assay; breast cancer; breast carcinoma; cancer cell; cancer cell culture; cancer growth; cancer regression; cell proliferation; chromatin immunoprecipitation; confocal microscopy; duolink assay; gene control; gene expression; gene sequence; genetic transcription; human; human cell; human cell culture; hypothesis; inhibition kinetics; mouse; nonhuman; nuclear localization signal; promoter region; receptor binding; Animals; Antineoplastic Agents, Hormonal; Breast Neoplasms; Carcinoma; Cell Proliferation; Chromatin Immunoprecipitation; Cyclin D1; Estradiol; Estrogen Receptor alpha; Female; Genes, myc; Humans; Mammary Neoplasms, Experimental; Medroxyprogesterone Acetate; Murinae; Progestins; Receptors, Progesterone; Transcription, Genetic |
| Año: | 2012 |
| Volumen: | 72 |
| Número: | 4 |
| Página de inicio: | 315 |
| Página de fin: | 320 |
| Título revista: | Medicina (Argentina) |
| Título revista abreviado: | Medicina |
| ISSN: | 00257680 |
| CODEN: | MEDCA |
| CAS: | fulvestrant, 129453-61-8; medroxyprogesterone acetate, 71-58-9; Antineoplastic Agents, Hormonal; Cyclin D1, 136601-57-5; Estradiol, 50-28-2; Estrogen Receptor alpha; Medroxyprogesterone Acetate, 71-58-9; Progestins; Receptors, Progesterone; fulvestrant, 22X328QOC4 |
| Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00257680_v72_n4_p315_Lanari |
Referencias:
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Citas:
---------- APA ----------
Lanari, C., Giulianelli, S., Vaqué, J.P., Wargon, V., Soldati, R., Vanzulli, S.I., Martins, R.,..., Gutkind, J.S. (2012) . The role of estrogen receptor alpha in breast cancer cell proliferation mediated by progestins . Medicina (Argentina), 72(4), 315-320.Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00257680_v72_n4_p315_Lanari [ ]
---------- CHICAGO ----------
Lanari, C., Giulianelli, S., Vaqué, J.P., Wargon, V., Soldati, R., Vanzulli, S.I., et al. "The role of estrogen receptor alpha in breast cancer cell proliferation mediated by progestins " . Medicina (Argentina) 72, no. 4 (2012) : 315-320.Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00257680_v72_n4_p315_Lanari [ ]
---------- MLA ----------
Lanari, C., Giulianelli, S., Vaqué, J.P., Wargon, V., Soldati, R., Vanzulli, S.I., et al. "The role of estrogen receptor alpha in breast cancer cell proliferation mediated by progestins " . Medicina (Argentina), vol. 72, no. 4, 2012, pp. 315-320.Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00257680_v72_n4_p315_Lanari [ ]
---------- VANCOUVER ----------
Lanari, C., Giulianelli, S., Vaqué, J.P., Wargon, V., Soldati, R., Vanzulli, S.I., et al. The role of estrogen receptor alpha in breast cancer cell proliferation mediated by progestins . Medicina. 2012;72(4):315-320.Available from: https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00257680_v72_n4_p315_Lanari [ ]
