REVERSION OF THE NEOPLASTIC PHENOTYPE OF HUMAN GLIOBLASTOMA CELLS BY CONNEXIN43 (CX43)

Connexins (cx), structural components of gap junction, are believed to play a role in the regulation of cell proliferation and suppression o f the neoplastic phenotype. We used human brain glioblastoma tumor cel ls 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 s everal human brain tumor cell lines examined. Transfection of human cx 43 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 es tablishment of gap junction communication in cx43 transfected cells. W e conclude that the loss of cx43 expression may play a role in the dev elopment of human gliomas and that cx43 acts as a tumor suppressor gen e to human glioblastoma.