Negative growth control of renal cell carcinoma cell by Connexin 32: Possible involvement of Her-2
Negative growth control of renal cell carcinoma cell by Connexin 32: Possible involvement of Her-2
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DOI：
10.1002/mc.20025
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发表时间：
2004-07-01
影响因子：
4.6
通讯作者：
Yano, T
中科院分区：
文献类型：
--
作者：
Fujimoto, E;Satoh, H;Yano, T
连接蛋白（Cx）基因具有一定的细胞特异性，对肿瘤细胞具有负性生长效应。我们以前曾报道，Cx 32在人肾细胞癌细胞（RCC）系以及肾脏的癌性区域中特异性下调，并且Cx在癌的祖细胞中表达。然而，Cx 32在RCC细胞生长控制中的确切作用仍然未知。在这项研究中，我们检测了Cx 32是否可以在针对人RCC细胞Caki-2细胞的生长控制中起作用。为了评估细胞生长控制，我们建立了具有Cx 32基因稳定表达的Caki-2细胞。Cx 32在Caki-2细胞中的表达诱导了生长的接触抑制和非锚定依赖性生长能力的降低，但并不显著影响滞后期生长速率。Cx 32的这种生长控制依赖于在高细胞密度下抑制细胞周期从G（1）期到S期的转变，以及与抑制Her-2活化相关的细胞周期转变的抑制。此外，通过短干扰RNA抑制Caki-2细胞中Cx 32的表达诱导了Her-2的激活。这些数据表明Cx 32对Caki-2细胞具有负生长控制，部分原因是抑制Her-2活化。(C)2004 Wiley-Liss，Inc.
Connexin (Cx) genes have negative growth effects on tumor cells with certain cell specificity. We have previously reported that Cx32 is specifically downregulated in human renal cell carcinoma cell (RCC) lines as well as cancerous regions of kidneys and that the Cx is expressed in the progenitor cells of the carcinoma. However, the precise role of Cx32 in growth control of RCC cells remains unknown. in this study, we examined whether Cx32 could act in growth control against a human RCC cell, Caki-2 cell. In order to estimate the cell growth control, we established Caki-2 cells that have stable expression of Cx32 genes. Cx32 expression in Caki-2 cells induced contact inhibition of growth and reduced anchorage-independent growth ability, but did not significantly affect lag phase growth rates. This growth control by Cx32 was dependent on the inhibition of the cell-cycle transition from G(1) to S phase at high cell density, and the inhibition of the cell-cycle transition related to the suppression, of Her-2 activation. Furthermore, the suppression of Cx32 expression in Caki-2 cells by short interfering RNA induced the activation of Her-2. These data suggest that Cx32 has negative growth control of Caki-2 cells, partly due to the inhibition of the Her-2 activation. (C) 2004 Wiley-Liss, Inc.