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

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


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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. Access through your institution Buy or subscribe This is a preview of subscription content, access via your


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* Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS DOWNREGULATION OF SBF2-AS1 FUNCTIONS AS A TUMOR SUPPRESSOR IN


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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). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * 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 * Faculty of Pharmaceutical Sciences, Chiba


University, 1-8-1 Inohana, Chuo, 260-8675, Chiba, Japan Eriko Fujimoto, Hiromi Sato, Etsuko Negishi & Koichi Ueno * Department of Pathology, Yokohama City University Medical School, 3-8


Fukuura, Kanazawa, 236-0004, Kanagawa, Japan Yoji Nagashima * Japan Human Sciences Foundation, 13-4 Nihonbashi-Kodenmacho, Chuo, 103-0001, Tokyo, Japan Hiromi Hagiwara * Department of


Pathology, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan Yasufumi Omori * Faculty of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda,


669-1337, yogo, Japan Hiroshi Yamasaki Authors * Eriko Fujimoto View author publications You can also search for this author inPubMed Google Scholar * Hiromi Sato View author publications


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Scholar * Koichi Ueno View author publications You can also search for this author inPubMed Google Scholar * Yasufumi Omori View author publications You can also search for this author


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Tomohiro Yano. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 21 April 2004 * Revised: 03 December 2004 *


Accepted: 06 December 2004 * Published: 14 March 2005 * Issue Date: 19 May 2005 * DOI: https://doi.org/10.1038/sj.onc.1208430 SHARE THIS ARTICLE Anyone you share the following link with will


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content-sharing initiative KEYWORDS * connexin32 * tumor suppressor gene * Src * VEGF * metastatic renal cell carcinoma