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Studies on the mechanism of apoptosis in bovine mammary epithelial cells

牛乳腺上皮细胞凋亡机制的研究

基本信息

批准号：
13660280
负责人：
HAGINO Akihiko
金额：
$ 2.11万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13660280/
关键词：
bovine mammary epithelial cells apoptosis butyric acid dexamethasone IGF IGFBPs 乳腺上皮細胞 IGFBP 乳腺細胞分化

项目摘要

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.

本研究的目的是：1)研究地塞米松对牛乳腺上皮细胞(BMEC)增殖的影响；2)研究丁酸ADID诱导的BMEC的凋亡；3)生长激素对BMEC中IGFBPs表达的影响。1)BMEC在含催乳素、胰岛素和地塞米松等促乳素激素的Matrigel上培养形成乳腺样结构，并在腔内分泌酪蛋白。2)丁酸可诱导乳源激素诱导的BMEC发生凋亡，而丁酸诱导分化前的BMEC未观察到这种作用。3)由于IGF/IGFBPs系统被认为在BMEC存活过程中起重要作用，因此用RT-PCR和Western Ligand印迹方法分别检测了IGF-I、IGF-I受体和IGFBP-3的mRNA和蛋白表达。结论：1)地塞米松是诱导分化的乳腺上皮细胞存活的重要因素之一，2)分化前后丁酸的诱导作用不同，3)IGF/IGFBPs系统在BMEC的凋亡中起重要作用，生长激素抑制IGFBP-5的表达。生长激素可能通过抑制IGFBP-5在BMEC中的表达而发挥细胞生存因子的作用，而IGFBP-5被认为通过抑制IGF-I的作用而诱导乳腺上皮细胞凋亡。