Expression Genetics of Hormone Dependent Human Tumors

Abstract

Proliferation of some cells in organs such as prostate, breast, and ovary is stimulated by hormones. The hormones function by binding to their receptors, thereby activating them to form complexes with other proteins. These complexes bind to response elements in DNA promoter regions and activate transcriptions of target downstream genes. For example androgen binds to the androgen receptor (AR) which then binds to the androgen response element (ARE) and activates transcription of a set of genes including prostate specific antigen (PSA). Growth of some tumors is hormone dependent, like the hormone dependent normal cells from which they were derived. But other tumors are hormone-unresponsive. For example, prostate tumors initially often are hormone dependent and respond to treatments based on drugs that block androgen production and function. But these tumors progress to develop hormone independence. About half of breast tumors are stimulated by estrogen (E) and the others are not. This property can be correlated in general with presence or absence, respectively, of the estrogen receptor (ER) (1,2). But about 40% of ER-positive breast tumors are not affected by E or antiestrogens such as Tamoxifen, thereby posing a serious clinical problem.

“Expression genetics is a conceptually different approach to the identification of cancer-related genes than the search for mutations at the genomic level.…Cancer geneticists have… ignored the productive potential of examining downstream events based on screening for differential gene expression.” R. Sager, 1997