title: Connexins in tumour suppression and cancer therapy.
abstract: Malignant cells usually show altered gap junctional intercellular communication and are often associated with aberrant expression or localization of connexins. Transfection of connexin genes into tumorigenic cells restores normal cell growth, suggesting that connexins form a family of tumour suppressor genes. Some studies have also shown that specific connexins may be necessary to control growth of specific cell types. Although we have found that genes encoding connexin32 (Cx32; beta 1), Cx37 (alpha 4) and Cx43 (alpha 1) are rarely mutated in tumours, our recent studies suggest that methylation of the connexin gene promoter may be a mechanism by which connexin gene expression is down-regulated in certain tumors. We have produced various dominant negative mutants of the genes encoding Cx26 (beta 2), Cx32 and Cx43, some of which prevent the growth control exerted by the corresponding wild-type genes. A decade ago, we proposed a method to enhance killing of cancer cells by diffusion of therapeutic agents through gap junctions. Recently, we and others have shown that gap junctional intercellular communication is responsible for the bystander effect seen in herpes simplex virus thymidine kinase/ganciclovir gene therapy. Thus, connexin genes can exert dual effects in tumour control: tumour suppression and a bystander effect for cancer therapy.
authors: Multistage Carcinogenesis Unit, International Agency for Research on Cancer, Lyon, France.
authors: H
authors: H
authors: Yamasaki
authors: Y
authors: Y
authors: Omori
authors: V
authors: V
authors: Krutovskikh
authors: W
authors: W
authors: Zhu
authors: N
authors: N
authors: Mironov
authors: K
authors: K
authors: Yamakage
authors: M
authors: M
authors: Mesnil
mesh_terms: D000818:Animals; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016296:Mutagenesis; D009369:Neoplasms / Q000235:genetics / Q000628:therapy
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26