Journal Article

Expression of hepaCAM is downregulated in cancers and induces senescence-like growth arrest via a p53/p21-dependent pathway in human breast cancer cells

Mei Chung Moh, Ting Zhang, Lay Hoon Lee and Shali Shen

in Carcinogenesis

Volume 29, issue 12, pages 2298-2305
Published in print December 2008 | ISSN: 0143-3334
Published online October 2008 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgn226
Expression of hepaCAM is downregulated in cancers and induces senescence-like growth arrest via a p53/p21-dependent pathway in human breast cancer cells

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

Previously, we reported the identification of a novel immunoglobulin-like cell adhesion molecule hepaCAM that is frequently downregulated and inhibits cell growth in hepatocellular carcinoma. In this study, we show that the expression of hepaCAM is suppressed in diverse human cancers. Aiming to evaluate the biological role of hepaCAM in breast cancer, we stably transfected the MCF7 cell line with either wild-type hepaCAM or its mutant hCAM-tailless that lacked the cytoplasmic domain. We found that hepaCAM inhibited colony formation and cell proliferation and arrested cells in the G2/M phase. Intriguingly, hepaCAM was capable of inducing cellular senescence as defined by the enlarged cell morphology and increased β-galactosidase activity. Furthermore, hepaCAM elevated the expression levels of senescence-associated proteins including p53, p21 and p27. In contrast, cell growth inhibition and senescence were less apparent in cells overexpressing hCAM-tailless mutant. To determine if the p53-mediated pathway was involved in hepaCAM-induced senescence, we used the small-interfering RNA system to knock down endogenous p53 expression. In the presence of hepaCAM, downregulation of p53 resulted in a clear reduction of p21, insignificant change in p27 and alleviated senescence. Together, the results suggest that the expression of hepaCAM in MCF7 cells not only inhibits cell growth but also induces cellular senescence through the p53/21 pathway.

Journal Article.  4512 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.