Profiling changes in gene expression during proliferation, differentiation, and apoptosis of human mammary epithelial cells using cDNA microarray

Abstract

The mammary gland undergoes striking changes in morphology and function during development and puberty and adult life. During each menstrual cycle, and particularly during pregnancy, mammary epithelial cells undergo cycles of proliferation, differentiation, and apoptotic cell death. During pregnancy, mammary epithelial cells proliferate and form lobulo-alveolar structures that prepare the gland for lactation (Traurig, H. H., 1967; Borst, D. W. et al., 1982; Zwierzchowski, L. et al., 1984). At late pregnancy, prior to parturition, breast epithelial cells cease proliferation and functionally differentiate into cells that express and secrete milk proteins. Throughout lactation, epithelial cells remain quiescent but continue to express milk proteins (Traurig, H. H., 1967). After weaning, the mammary gland undergoes involution, a phase of extensive remodeling characterized by degradation of ECM and epithelial cell death by apoptosis. The molecular mechanisms that regulate and coordinate the changes in mammary epithelial cell phenotypes are poorly understood. Genes that are up- or down-regulated at different developmental stages have been identified, but little is known about how they are regulated and coordinated. In this study, we made a novel cell culture model for studying proliferation, differentiation and apoptosis in the human mammary epithelial cells. Proliferation, differentiation, apoptosis of human mammary epithelial cells was induced by using specific hormones, starvation, and apoptosis inducer. To identify physiologically specific gene expression patterns in human mammry epithelial cells was used cDNA microarrays. Analysis of gene expression changes at the RNA level using cDNA against an array of 8286 human genes showed that 7935 (95%) of genes were expressed in the HMEC. A total of 388 genes (4.6%) were found to be regulated during HMEC differentiaton. A total of 411genes (4.9%) were found to be regulated during HMEC apoptosis by serum-free medium. A total of 119 genes (1.4%) were found to be regulated during HMEC apoptosis by anti-Fas antibodies. We were performed by bioinformatics program, to search for the functions of genes identified by cDNA microarrays.