BRCA1 has been characterized as one of the major breast cancer susceptibility genes. Although no BRCA1 mutations have been reported in sporadic breast cancer, altered levels of BRCA1 are found in non hereditary breast malignant lesions. Therefore, BRCA1 is potentially playing a key role in the genesis of breast cancer. In this study, we explored the effects of estradiol and two differentiating agents, the progestin ORG2058 and retinoic acid, on BRCA1 mRNA expression in human estrogen and progesterone receptor positive MCF-7 cells. Using RNAse protection assay, we have demonstrated that ORG2058 induces a major (50 times) stimulation of BRCA1 mRNA expression. The maximum induction effect was obtained at the pharmacological dose of 100 nM and after 48 h of treatment. While estradiol generated an expected increase of BRCA1 mRNA, retinoic acid did not produce any effects. Our results demonstrate for the first time that BRCA1 is specifically up-regulated by a progestin, a steroid known to induce the differentiation of epithelial mammary cells. The absence of retinoic acid effect suggests that a specific progesterone-dependent pathway, could control BRCA1 expression.

The progestin ORG2058 but not retinoic acid stimulates BRCA1 mRNA expression in MCF-7 human breast cancer cells.

BEVILACQUA, GENEROSO;
1997-01-01

Abstract

BRCA1 has been characterized as one of the major breast cancer susceptibility genes. Although no BRCA1 mutations have been reported in sporadic breast cancer, altered levels of BRCA1 are found in non hereditary breast malignant lesions. Therefore, BRCA1 is potentially playing a key role in the genesis of breast cancer. In this study, we explored the effects of estradiol and two differentiating agents, the progestin ORG2058 and retinoic acid, on BRCA1 mRNA expression in human estrogen and progesterone receptor positive MCF-7 cells. Using RNAse protection assay, we have demonstrated that ORG2058 induces a major (50 times) stimulation of BRCA1 mRNA expression. The maximum induction effect was obtained at the pharmacological dose of 100 nM and after 48 h of treatment. While estradiol generated an expected increase of BRCA1 mRNA, retinoic acid did not produce any effects. Our results demonstrate for the first time that BRCA1 is specifically up-regulated by a progestin, a steroid known to induce the differentiation of epithelial mammary cells. The absence of retinoic acid effect suggests that a specific progesterone-dependent pathway, could control BRCA1 expression.
1997
Caligo, Ma; Bellachene, A; Cipollini, G; Bevilacqua, Generoso; Castronovo, V.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/48067
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact