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[Cancer Research 58, 5089-5096, November 15, 1998]
© 1998 American Association for Cancer Research

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Reversion of the Neoplastic Phenotype of Human Glioblastoma Cells by Connexin 43 (cx43)1

Ruo-Pan Huang2, Yan Fan, Mohammad Z. Hossain, Ao Peng, Zi-Li Zeng and Alton L. Boynton

Molecular Medicine, Northwest Hospital, Seattle, Washington 98125 [R-P. H, Y. F., M. Z. H., A. P., Z-L. Z., A. L. B.], and Shantou University Medical College, Shantou City, Guangdong Province, People's Republic of China, 51503 [Z-L. Z.]

Connexins (cx), structural components of gap junction, are believed to play a role in the regulation of cell proliferation and suppression of the neoplastic phenotype. We used human brain glioblastoma tumor cells as a model system to test this hypothesis. Western blot and reverse transcription-PCR analysis indicate that the expression levels of the gap junction protein connexin 43 (cx43) are profoundly decreased in several human brain tumor cell lines examined. Transfection of human cx43 into human glioblastoma cell lines U251 and T98G profoundly reduces cell proliferation in monolayer culture, in soft agar, and in athymic nude mice. Surprisingly, these effects are not associated with the establishment of gap junction communication in cx43 transfected cells. We conclude that the loss of cx43 expression may play a role in the development of human gliomas and that cx43 acts as a tumor suppressor gene to human glioblastoma.

1 This work was supported by NIH Grants CA39745 and CA57064 (both to A. L. B.).

2 To whom requests for reprints should be addressed, at Molecular Medicine, Northwest Hospital, 120 Northgate Plaza, Suite 230, Seattle, WA 98125. Phone: (206) 368-3063; Fax: (206) 368-3009; E-mail: rphuang@nwlink.com or rhuang@nwhsea.org.

Received 4/29/98. Accepted 9/17/98.




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