【摘 要】
：
Differentiation of monolayered epithelia is characterized by the formation of a basoapical polarity axis.In ducts and glands, apical polarity results from the positioning of tight junctions at the ape
【机 构】
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Department of Basic Medical Sciences Purdue University USA
【出 处】
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(BITs 3rd Annual World Cancer Congress-2010, Breast Cancer C
论文部分内容阅读
Differentiation of monolayered epithelia is characterized by the formation of a basoapical polarity axis.In ducts and glands, apical polarity results from the positioning of tight junctions at the apex of cells, against the lumen.Using mammary glandular structures (acini) produced in three-dimensional cell culture we have demonstrated that, in order for mammary epithelial cells to exit quiescence and enter the cell cycle, acini have to lose apical polarity.We have also identified alterations in apical polarity that occurs early on during cancer development.Our hypothesis is that a set of genes dependent on apical polarity status is controlling quiescence and possibly other important features involved in tumorigenesis.Using Affymetrix technology we have performed microarray analysis on the 22,277 features/genes of the Human Genome U133A 2.0 array Chip with four biological replicates of mammary acini with full basoapical polarity compared to acini treated with two different methods to specifically alter apical polarity.Results from robust statistical analysis resulted in 30 genes that were found to be commonly and significantly down-regulated in cells with altered apical polarity compared to control.Only one gene codes for a known tight junction protein ZO-3; other genes belong to transcriptional regulation, signal transduction, chromatin remodeling, DNA repair and apoptosis control.Among these genes several have been shown to be transcriptionally down-regulated in breast cancer and/or are related to proliferation control.Other genes, notably a gene coding for a SWI-SNF component involved in chromatin remodeling appear like new potential targets for breast cancer.Thus, apical polarity loss, which is a common phenomenon in breast cancer development, might impact multiple mechanisms, including gene expression control, involved in tumorigenesis.
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