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Connexin32 as a tumor suppressor gene in a metastatic renal cell carcinoma cell line

Oncogene volume 24, pages 3684–3690 (2005)Cite this article

Abstract

Connexin genes expressing gap junction proteins have tumor-suppressive effects on primary cancers with certain cell specificity, but the suppressive effects on metastatic cancers are still conflicting. In this study, we show that connexin32 (Cx32) has a strong tumor-suppressive effect on a human metastatic renal cell carcinoma cell line (Caki-1 cell). Cx32 expression in Caki-1 cells reduced in vitro malignant phenotypes of the cells such as anchorage independency and invasion capacity. Furthermore, the Cx32 expression drastically reduced the development of Caki-1 cells in nude mice. We also determined that Cx32 reduced the malignant phenotypes in Caki-1 cells mainly through the inactivation of Src signaling. Especially, Cx32-dependent inactivation of Src decreased the production of vascular epithelial growth factor (VEGF) via the suppression of signal transducers and activators of transcription 3 (Stat3) activation, and we confirmed this result using short interfering RNA. In nude mice, Cx32-transfected Caki-1 cells showed lower serum level of VEGF comparing mock transfectant, and the development of the cells in nude mice positively related to the VEGF level. These data suggest that Cx32 acts as a tumor suppressor gene in Caki-1 cells and that the tumor-suppressive effect partly depends on the inhibition of Src-Stat3-VEGF signal pathway.

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Acknowledgements

We are grateful to Miss Haruna Satoh for her technical assistance. This work was supported by a grant on Health Sciences Focusing on Drug Innovation from the Japan Health Sciences Foundation (SH24209 and KH 21012).

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Authors and Affiliations

  1. Department of Food Science Research for Health, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku, 162-8636, Tokyo, Japan

    Eriko Fujimoto, Hiromi Sato, Sumiko Shirai, Keiko Fukumoto, Hiromi Hagiwara, Kiyokazu Hagiwara & Tomohiro Yano

  2. Faculty of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo, 260-8675, Chiba, Japan

    Eriko Fujimoto, Hiromi Sato, Etsuko Negishi & Koichi Ueno

  3. Department of Pathology, Yokohama City University Medical School, 3-8 Fukuura, Kanazawa, 236-0004, Kanagawa, Japan

    Yoji Nagashima

  4. Japan Human Sciences Foundation, 13-4 Nihonbashi-Kodenmacho, Chuo, 103-0001, Tokyo, Japan

    Hiromi Hagiwara

  5. Department of Pathology, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan

    Yasufumi Omori

  6. Faculty of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, 669-1337, yogo, Japan

    Hiroshi Yamasaki

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  1. Eriko Fujimoto
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Correspondence to Tomohiro Yano.

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Fujimoto, E., Sato, H., Shirai, S. et al. Connexin32 as a tumor suppressor gene in a metastatic renal cell carcinoma cell line. Oncogene 24, 3684–3690 (2005). https://doi.org/10.1038/sj.onc.1208430

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