Estrogen regulation of p53 isoforms in the human breast cancer cell line MCF7.

Abstract

Abstract Abstract #4067 Background: p53, a transcription factor activated in response to different cellular stresses, is involved in the majority of cancers. Recently, we have shown that the p53 gene, due to alternative splicing, encodes for 9 different p53 proteins (isoforms) expressed in a tissue-dependent manner. Moreover, p53 isoforms bind preferentially some p53 target gene promoters, increasing the complexity of the p53 pathway. Preliminary results indicate that p53 isoforms are differentially expressed in breast tumours and are associated with survival.
 Methods and Results: As some p53 isoform expression is also associated with ERa status in breast cancer, we aimed to investigate the effect of 17b-estradiol (E2) on the expression of p53 isoforms in MCF7 cells. We observed that E2 regulated the expression of the p53b isoforms at the protein level but not at the mRNA level. To investigate whether E2 confers resistance to genotoxic stress, we treated cells with doxorubicin, a commonly used chemotherapeutic agent. E2 sensitises MCF7 cells to doxorubicin treatment after a long exposure (3 days). However, we observed that E2 protects MCF7 cells from cell death following short exposure (1 hour) to doxorubicin in a p53-dependent manner. p53 isoforms are differentially expressed after 1h or 3 days treatment with doxorubicin, suggesting their involvement in the response to doxorubicin. These data are consistent with our findings in primary breast cancer, linking p53 isoforms to prognosis.
 Conclusion: Our data demonstrated that E2 may influence p53 isoforms and response to doxorubicin in breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4067.