Expression and Activation of STAT Transcription Factors in Breast Cancer
Uniformed Services University Of The Health Sciences Bethesda United States
Pagination or Media Count:
Endocrine therapy has proven a valuable approach to the treatment of breast cancer. In particular, antiestrogens have demonstrated significant improvement in survival rates, and have recently been shown to prevent breast cancer development in women in high-risk populations. Other endocrine or cytokine-based therapies, including glucocorticoids and interferons, which have been highly effective as adjuvant treatment of hematological cancers, have also shown promise in breast cancer. However, due to the less consistent clinical responses to both glucocorticoids and interferons in breast cancer patients, research efforts have continued to focus on improving their efficiency. Important recent insights into the underlying molecular biology of hormone signal transduction have identified the critical involvement of cytoplasmic STAT transcription factors. These molecular intermediaries convey the signal from the cell surface to the nucleus where they activate transcription of tar get genes. One hormone, which signals via the STAT pathway, is of particular relevance in breast cancer namely, the mammary growth and differentiation factor, prolactin. The specific aims of this study were 1 to examine whether the glucocorticoid, dexamethasone, may promote the terminal differentiation of breast cancer cells by stimulating prolactin activation of the transcription factors, STAT5a and STAT5b 2 to examine whether prolactin interferes with type I interferon signal transduction by competing for limited cytoplasmic STAT factors, thus antagonizing the antiproliferative effect of type Iinterferons in breast cancer treatment and 3 to test if mammary tumor cell lines, like many hematopoietic cancer cells, become sensitized to the anti-proliferative effect of type I interferons by pretreatment with interferon-gamma.