Reversion of the Neoplastic Phenotype of Human Glioblastoma Cells by Connexin 43 (CX43)1

Connexins (ex), 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 tran scription-PC K 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 I 251 and T9SG 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 glioblas toma. cells (10). cx43 may also be involved in the regulation of cell cycle progression (8). Brain tumors are one of the leading causes of death among young children and adults. Glioblastomas are the most common primary brain tumors and are among the deadliest of tumors: most of the 20,000 people diagnosed each year in the United States with this form of brain cancer die within 2 years. To explore the possible role of cx43 in brain tumors, we first examined the expression levels of cx43 in brain tumor cells and also transfected cx43 into human glioblastoma cells. Our results show that expression of cx43 is decreased in human brain tumor cell lines. Transfection of the cx43 gene into human glioblastoma cells reverses the transformed phenotype of these tumor cells. Furthermore, it is likely that the tumor suppression by cx43 is not directly related to GJC.