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The Role of ΔFosB on the Pro-survival Effect of PTHrP in Goat Mammary Epithelial Cells

Li, Hui, Yao, Xiaotong, Li, Lihui, Zheng, Huiling
Applied biochemistry and biotechnology 2016 v.180 no.4 pp. 707-716
alternative splicing, apoptosis, breast neoplasms, cell proliferation, cell viability, epithelial cells, genes, goats, mammary glands, messenger RNA, mice, neoplasm cells, osteosarcoma, proliferating cell nuclear antigen
The mechanism of regulation mammary epithelial cell number in ruminant is not fully understood, but is thought to be dependent on the balance of cell proliferation and cell apoptosis. Parathyroid hormone-related protein (PTHrP) could express in mammary epithelial cells and breast cancer cells, and has been reported to regulate cell survival. Here, we showed that PTHrP induced cell proliferation and increased the expression of CyclinD1 and proliferating cell nuclear antigen (PCNA) in goat mammary epithelial cells (GMEC). PTHrP increased the mRNA levels of anti-apoptosis genes Bcl-2 and Bcl-xl, and protected GMEC from apoptosis. We also found ΔFosB, an alternative splicing of finkel-biskis-jinkins murine osteosarcoma B (fosB), inhibited GMEC apoptosis, and induced cell proliferation with increased Bcl-2/Bax and Bcl-xl/Bax ratios. Interestingly, ΔFosB could further promote the pro-survival effect of PTHrP, and the Bcl-2/Bax and Bcl-xl/Bax ratios showed higher levels. We conclude that the pro-survival role of PTHrP in GMEC may be regulated by ΔFosB.