Expression of glucocorticoid and progesterone nuclear receptor genes in archival breast cancer tissue

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Expression of glucocorticoid and progesterone nuclear receptor genes in archival breast cancer tissue

Publisher
BioMed Central
Publication Date
Nov 07, 2002
Source
PMC
Keywords
Disciplines
  • Biology
  • Ecology
  • Geography
  • Medicine
License
Unknown

Abstract

Introduction Breast cancer is the most common malignancy in women in the Western world, with an incidence approaching 1/10 individuals in the USA in 1980 [1] and 1/11 in Australia in 1991. Several genetic and environmental risk factors have already been identified, particularly for cancers with a familial basis, including mutations within the BRCA1 and BRCA2 genes [2]. Other risk factors include a maternal relative with breast cancer, longer reproductive span, obesity, reproductive history and previous breast cancers [3]. Individual breast tumours are placed into one of three histological grades. These grades are representative of the degree of loss of differentiation and the acquisition of various mutations [4]. Thus, higher grade tumour cells will show fewer of the visual and functional characteristics of the cell type from which they were derived. However, cancer grade is only a rough guide to the state of any given tumour, because the biology of cancer varies wildly from one tumour to the next. The nuclear receptor genes are an extremely large family of genes that encode similar molecules, which bind to various messenger molecules and are typically found at or near the nuclear membrane [5]. The steroid nuclear receptors are a subfamily of the nuclear receptors that bind specifically to steroid hormones. Steroid receptors consist of highly conserved DNA and ligand binding domains, and a mutable hinge region connecting the two [6]. Once the hormone for the specific receptor binds, the receptor molecule moves across the nuclear mem- brane and binds to a specific hormone response element, which is a specialized sequence, on the tar- geted genes [5]. Once bound to its target genes, the receptor complex upregulates or downregulates the tran- scription of those genes in a specific manner. Activated steroid receptors affect many genes that are involved in cellular metabolism and often affect the transcription of other steroid receptors [7]. The overall action of any steroid receptor pathway is rar

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