Glucocorticoid-dependent BCL-X gene expression during involution of normal mammary gland

PAOLA BERTUCCI; LUCIANA ROCHA VIEGAS; EDITH KORDON; ADALI PECCI

Rosario, Santa Fe

Congreso; XLII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2006

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

bcl-X gene is highly related to bcl-2 and generates at least five different isoforms which are products of alternative splicing of an unique gene. The 5’-region of the mouse bcl-X gene contains at least five different promoters which are activated in a tissue-specific pattern of promoter usage. The steroid hormone dexamethasone (dex) has demonstrated to be able to control bcl-X expression and to influence the ratio between the isoforms bcl-XL (antiapoptotic) and bcl-XS (proapoptotic) in different tissues. This hormone effect occurs mainly through the control of bcl-XL expression. According to previous reports, there is a decrease in the ratio bcl-XL/bcl-XS of normal mammary gland 48 h after weaning. In the present work we explored the potential regulation of bcl-X gene by glucocorticoids during involution of mammary tissue. By RT-PCR, our preliminary results show that bcl-XL mRNA levels are increased during involution upon dex treatment as compared with non-treated animals. Moreover, transcripts generated from promoters P1 and P4 are drastically decreased in those animals. On the other hand, we found that Lif expression and p-STAT3 did not change with treatment. This observation correlates with an increase in glucocorticoid receptor analysed by western blot, suggesting that a download of GR during involution may be responsible for the decreased of the antiapoptotic isoform.