Studies on the mechanism of apoptosis in bovine mammary epithelial cells

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The objectives of this study were : 1) to determine the effect of dexamethasone on the proliferation of bovine mammary epithelial cells (BMEC), 2) to evaluate an apoptosis of BMEC induced by butyric adid, and 3) to assess the impact of growth hormone on IGFBPs expression in BMEC.1) BMEC formed mammosphere-like structure when cultured on Matrigel with lactogenic hormones (prolactin, insulin and dexamethasone) and secreted casein in the lumen. Although the mammosphere-like structure was broken and an apoptosis was occurred after removal of lactogenic hormones, dexamethasone, not prolactin, inhibited the apoptosis.2) Butyrate induces apotosis of BMEC differentiated by lactogenic hormones, whereas the apoptic effect was not observed in BMEC before the differentiation.3) Since IGF/IGFBPs system is considered to play a important role in cell survival in BMEC, IGF-I, IGF-I receptor and IGFBP-3, -5 mRNA and protein expression, was determined by RT-PCR and western ligand blot, respectively.IGFBP-5 expression was decreased by growth hormone and lactogenic hormones. In conclusion, 1) dexamethasone is one of the most important factor of cell survival in differentiated mammary epithelial cells, 2) apoptic effect of butyrate is different between before and after differentiation of BMEC, and 3) IGF/IGFBPs system plays an important role in apoptosis of BMEC and growth hormone inhibited the expression of IGFBP-5. Growth hormone may act as a cell-survival factor by inhibiting the expression of IGFBP-5 in BMEC, which is considered to induce apoptosis of mammary epithelial cells by inhibiting the action of IGF-I.