Journal Article

Delayed liver regeneration and increased susceptibility to chemical hepatocarcinogenesis in transgenic mice expressing a dominant-negative mutant of connexin32 only in the liver

Maria Lúcia Zaidan Dagli, Hiroshi Yamasaki, Vladimir Krutovskikh and Yasufumi Omori

in Carcinogenesis

Volume 25, issue 4, pages 483-492
Published in print April 2004 | ISSN: 0143-3334
Published online April 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh050
Delayed liver regeneration and increased susceptibility to chemical hepatocarcinogenesis in transgenic mice expressing a dominant-negative mutant of connexin32 only in the liver

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

A growing body of evidence from in vitro studies indicates that gap junction proteins connexins may have a tumor-suppressor function. Our previous double transfection experiments on HeLa cells have shown that a dominant-negative mutant V139 M of connexin32 (Cx32) can abolish gap junctional intercellular communication (GJIC). To examine whether the same dominant-negative mutant of Cx32 inhibits GJIC between hepatocytes in vivo and thus modulates cell proliferation and susceptibility to hepatocarcinogenesis, we created transgenic mice with the mutant Cx32 gene driven by a liver-specific albumin promoter. These mice developed normally both before and after birth, and GJIC in their liver was diminished, as expected. No increase in incidence of spontaneous tumors of any site was observed in the transgenic mice. Rather unexpectedly, cell proliferation during liver regeneration after partial hepatectomy was retarded by 24 h in the transgenic mice compared with the wild-type mice. In contrast, the transgenic male mice were more susceptible to diethylnitrosamine-induced hepatocarcinogenesis, developing more liver tumors with shorter latency. These results show that GJIC can coordinate cell growth both positively and negatively in vivo, supporting the idea that GJIC is essential for maintenance of homeostasis.

Keywords: BrdU, bromodeoxyuridine; Cx, connexin; DEN, diethylnitrosamine; GJIC, gap junctional intercellular communication; LY, Lucifer yellow; TCPOBOP, 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene

Journal Article.  6221 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.