Mechanism of Aromatic Hydrocarbon Induced Mammary Tumorigenesis.
Annual rept. 30 Sep 96-29 Sep 97
BOSTON UNIV MA
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Recent evidence suggests that the rise in breast cancer rates reflects increased exposure to and bioaccumulation of environmental pollutants, such as 7,12-dimethylbenzaanthracene DMBA. Female Sprague-Dawley rats treated with DMBA develop mammary breast tumor by about 15 weeks. Mere experiments were proposed to elucidate the roles of the aromatic hydrocarbon Ah and estrogen receptors and the c-myc oncogene. Changes in the expression and function of these genes in normal and malignant tissue, and the regulation of any altered phenotype would be evaluated. Towards these goals, inappropriate activation of the NF-kBRel family of factors, which regulates c-myc expression, has been discovered in the rat breast neoplasias. Furthermore, NF-kBRel serves as a survival factor for breast cancer cells in vitro. Work, in progress, to address the temporal relationship between expression of these various genes and neoplastic transformation of mammary cells, has shown NF-kBRel activation precedes tumor formation. These findings suggest a potential mechanism for aberrant regulation of c-myc expression in breast cancer and for new therapeutic approaches.
- Anatomy and Physiology
- Medicine and Medical Research