Gap junction genes Cx26 and Cx43 individually suppress the cancer phenotype of human mammary carcinoma cells and restore differentiation potential

Karen K. Hirschi, Cheng En Xu, Tetsuya Tsukamoto, Ruth Sager

研究成果: ジャーナルへの寄稿学術論文査読

257 被引用数 (Scopus)

抄録

Normal human mammary epithelial cells express hCx43 and hCx26 proteins, which form functional gap junction channels. Both Cx genes are transcriptionally down-regulated in mammary carcinoma cell lines; consequently, no protein is made and gap junctions are absent. This result suggests that the loss of gap junctional communication may play an important role in carcinogenesis. To address this question, two sets of stable transfectants were produced in a recloned line of human mammary carcinoma cells (MDA-MB-435). One set expressed hCx26, and the other expressed hCx43. Studies of transfectants that contain functional gap junctions showed that they grew more slowly in culture than controls, and that their tumor-forming ability was strongly suppressed. In studies designed to examine their differentiation capacity, these transfectants were found to have regained the capacity to form three-dimensional structures in a matrigel matrix. This property is characteristic of normal mammary epithelial cells, but it is lost in the parental tumor cells and neo-transfectant controls. Thus, junctional communication is shown here to play a decisive role in the morphogenesis of mammary gland structures. The hCx26 and hCx43 genes behave as classical tumor suppressor genes both in culture and in animal tests in restoring growth regulatory properties to metastatic mammary carcinoma cells. Expression of these genes further induces the ability to differentiate as shown by the formation of three-dimensional structures when transfected cells are embedded in a matrigel matrix. These findings suggest that the reexpression of gap junctions may play a vital role in normalizing tumor cell behavior.

本文言語英語
ページ(範囲)861-870
ページ数10
ジャーナルCell Growth and Differentiation
7
7
出版ステータス出版済み - 1996
外部発表はい

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 細胞生物学

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