Aberrant Homeobox Gene Expression in Mammary Tumorigenesis.

摘要

We hypothesized that aberrant expression of Hox genes in mammary epithelial cells results in the inappropriate regulation of a wide variety of Hox target genes; this could lead to a change from a normal to a preneoplastic, or from a preneoplastic to a neoplastic phenotype. The purpose of this proposal is to test this hypothesis by manipulating the expression of Hox genes such as Hoxal, Hoxa51 or Hoxa11 in cells from hyperplastic (preneoplastic) lesions of the breast by employing a tetracycline regulated vector system. The goals of this research are: (1) to understand the functions of homeobox genes in normal and neoplastically transformed mammary epithelial cells; (2) to ascertain whether or not the overexpression of homeobox genes results in a neoplastic phenotype; and (3) to assess whether these Hox gene overexpressing cells respond to exogenous RA. In the past year, we analyzed and compared both p53+/+ and p53- /- breast tumors for Hox gene expression. In addition, we examined the influences of pituitary hormones and the carcinogen, DMBA, on Hox A cluster gene expression. Further, we also established a tetracycline inducible Hoxal overexpressing cell line. This new data is significant in that it may be employed to develop novel methods for regulating homeobox gene expression as a therapy for human breast cancer.