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Induction of a bystander effect in HeLa cells by using a bigenic vector carrying viral thymidine kinase and connexin32 genes
Author(s) -
Tanaka Toshiaki,
Yamasaki Hiroshi,
Mesnil Marc
Publication year - 2001
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.1026
Subject(s) - bystander effect , hela , connexin , biology , thymidine kinase , gap junction , transfection , ganciclovir , suicide gene , cell culture , microbiology and biotechnology , cancer research , intracellular , virology , gene , immunology , herpes simplex virus , genetic enhancement , virus , genetics , human cytomegalovirus
We previously showed that gap junction intercellular communication mediates the bystander effect in anticancer gene therapy with the herpes simplex virus thymidine kinase (HSV‐tk) and ganciclovir. Because most cancer cell lines have lost their ability to communicate through gap junctions, we investigated whether we could induce such a communication by transferring a gene for a gap junction. We transfected a vector carrying the HSV‐tk (t k ) and gap junction (connexin (Cx) 32) genes (Cx32 + tk + ) into noncommunicating HeLa cells. We compared the cytotoxicity of ganciclovir with mixtures of these cells and HeLa cells that expressed (Cx32 + ) or did not express (Cx32 − ) the Cx32 gene. The bystander effect was strong when the two mixed cell types expressed Cx32 (i.e., Cx32 + tk + cells and Cx32 + tk − cells). Only 25% of cells survived in this communicating mixture, even when only 10% of the cells were Cx32 + tk + . There was also a moderate bystander effect when the Cx32 + tk + cells were mixed with noncommunicating HeLa cells in a 50% ratio. These results demonstrated that the bystander effect is enhanced by Cx32 and suggested that expression of Cx in only one cell type in a mixture can cause a bystander effect. Mol. Carcinog. 30:176–180, 2001. © 2001 Wiley‐Liss, Inc.