Gene expression during active cell death in involuting prostate and mammary gland: Cloning and characterization of regression-selected genes (RSG).

Title: Gene expression during active cell death in involuting prostate and mammary gland: Cloning and characterization of regression-selected genes (RSG).
Authors: Guenette, Robert S.
Date: 1995
Abstract: Following hormonal ablation in the rat ventral prostate (via castration) or rat mammary gland (after weaning) the epithelial cells of both glands are eliminated by active cell death during the regression of the glands. Several genes including TRPM-2, (testosterone repressed prostate message), RVP.1, fos, and myc, have been shown to be induced in the prostate during this process. We have investigated the expression of several other genes that may be associated with apoptosis, including tissue transglutaminase (tTGase), poly (ADP-ribose) polymerase (PARP), and heat shock protein 27 (Hsp27). Northern hybridization has been used to determine the steady-state mRNA levels of these genes in both the regressing prostate and mammary glands. The time course of induction has been compared to changes in the steady state levels of several control genes including prostate steroid binding protein (PSBP) (prostate), $\beta$-casein (mammary), $\alpha$-tubulin, and TRPM-2 (both prostate and mammary). A novel cross-screening approach first described by Wong et al., 1989 was used to clone and characterize genes other than those described above which were induced during the regression of both rat prostate and mammary gland. Two regression selected genes (RSG) refered to as RSG-2, and RSG-8, were isolated, and their role in the active cell death process has been investigated. RSG-2 is homologous to cathepsin B, a thiol protease that has been previously identified as one of the extracellular proteases that is activated in metastatic cells. RSG-8, is homologous to rat insulin like growth factor binding protein 5 (IGFBP-5), a member of a group of six related proteins that are known to mediate the effects of the growth factors IGF-I, and IGF-II. The steady state level of IGFBP-5 mRNA in the normal prostate is low but detectable. In the regressing prostate, the mRNA for IGFBP-5 mRNA is induced and its steady state peaks in the luminal epithelial cells of the prostate that undergo active cell death (ACD) between 3 and 4 days after castration. The gene is induced in a similar fashion in the regressing mammary gland following weaning. The expression of another IGFBP, namely IGFBP-2 contrasts that of IGFBP-5, with a high steady state level in both prostate and mammary gland, which increase only slightly during the regression process. The increase in mRNA steady-state levels for both IGFBP-2 and IGFBP-S were shown by in-situ hybridization to localize to the epithelial cells that are deleted during the regression process. The differential expression of IGFBP-2 and IGFBP-5 suggest that modulating the epithelial cells response to the IGF growth factors may influence the active cell death process in hormonally dependent tissues such as the prostate and mammary gland. (Abstract shortened by UMI.)
CollectionTh├Ęses, 1910 - 2010 // Theses, 1910 - 2010
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