Vitamin D3 regulates the formation and degradation of gap junctions in androgen-responsive human prostate cancer cells.
Vitamin D3 regulates the formation and degradation of gap junctions in androgen-responsive human prostate cancer cells.
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DOI：
10.1371/journal.pone.0106437
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Mehta PP
中科院分区：
文献类型：
--
作者：
Kelsey L;Katoch P;Ray A;Mitra S;Chakraborty S;Lin MF;Mehta PP
1α-25（OH）2维生素D3（1- 25 D）是维生素D3的一种活性激素形式，是一种众所周知的化学预防和促分化剂。它已被证明可以抑制几种前列腺癌细胞系的生长。间隙连接由称为连接蛋白（Cx）的蛋白质形成，是细胞-细胞通道的集合体，其允许相邻细胞之间交换小的生长调节分子。缝隙连接通道介导的细胞间通讯是调节细胞生长和分化的重要稳态调控机制。我们已经研究了1- 25 D对雄激素反应性前列腺癌细胞系LNCaP中间隙连接的形成和降解的影响，LNCaP表达逆转录病毒引入的Cx 32。连接蛋白32由正常前列腺和前列腺肿瘤的管腔和高度分化的细胞表达。我们的研究结果表明，1- 25 D增强了Cx 32的表达及其随后组装成间隙连接。我们的研究结果进一步表明，1- 25 D阻止雄激素调节的Cx 32降解，在绝经后，独立于雄激素受体（AR）介导的信号传导。最后，我们的研究结果表明，间隙连接的形成使表达Cx 32的LNCaP细胞对1- 25 D的生长抑制作用敏感，并改变了它们的形态。这些发现表明，1- 25 D在LNCaP细胞中的生长抑制作用可能与其调节Cx 32组装成间隙连接的能力有关。
1α-25(OH)2 vitamin D3 (1-25D), an active hormonal form of Vitamin D3, is a well-known chemopreventive and pro-differentiating agent. It has been shown to inhibit the growth of several prostate cancer cell lines. Gap junctions, formed of proteins called connexins (Cx), are ensembles of cell-cell channels, which permit the exchange of small growth regulatory molecules between adjoining cells. Cell-cell communication mediated by gap junctional channels is an important homeostatic control mechanism for regulating cell growth and differentiation. We have investigated the effect of 1-25D on the formation and degradation of gap junctions in an androgen-responsive prostate cancer cell line, LNCaP, which expresses retrovirally-introduced Cx32. Connexin32 is expressed by the luminal and well-differentiated cells of normal prostate and prostate tumors. Our results document that 1-25D enhances the expression of Cx32 and its subsequent assembly into gap junctions. Our results further show that 1-25D prevents androgen-regulated degradation of Cx32, post-translationally, independent of androgen receptor (AR)-mediated signaling. Finally, our findings document that formation of gap junctions sensitizes Cx32-expressing LNCaP cells to the growth inhibitory effects of 1-25D and alters their morphology. These findings suggest that the growth-inhibitory effects of 1-25D in LNCaP cells may be related to its ability to modulate the assembly of Cx32 into gap junctions.
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影响因子：
10.3
作者：
Ahn, Jiyoung;Peters, Ulrike;Hayes, Richard B.
通讯作者：
Hayes, Richard B.
影响因子：
3.3
作者：
Govindarajan R;Chakraborty S;Johnson KE;Falk MM;Wheelock MJ;Johnson KR;Mehta PP
通讯作者：
Mehta PP
DOI：
10.1083/jcb.113.2.371
发表时间：
1991-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mehta PP;Loewenstein WR
通讯作者：
Loewenstein WR
影响因子：
4.8
作者：
Govindarajan, R;Zhao, S;Mehta, PP
通讯作者：
Mehta, PP
影响因子：
4.8
作者：
Blutt, SE;Allegretto, EA;Weigel, NL
通讯作者：
Weigel, NL