Breast Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Breast Cancer, including details on symptoms, genetics, screening, treatment, information.

HIN-1, an inhibitor of cell growth, invasion, and AKT activation.

Krop I, Parker MT, Bloushtain-Qimron N, Porter D, Gelman R, Sasaki H, Maurer M, Terry MB, Parsons R, Polyak K

Department of Medical Oncology and Biostatistics, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

The HIN-1 gene encoding a small, secreted protein is silenced due to methylation in a substantial fraction of breast, prostate, lung, and pancreatic carcinomas, suggesting a potential tumor suppressor function. The receptor of HIN-1 is unknown, but ligand-binding studies indicate the presence of high-affinity cell surface HIN-1 binding on epithelial cells. Here, we report that HIN-1 is a potent inhibitor of anchorage-dependent and anchorage-independent cell growth, cell migration, and invasion. Expression of HIN-1 in synchronized cells inhibits cell cycle reentry and the phosphorylation of the retinoblastoma protein (Rb), whereas in exponentially growing cells, HIN-1 induces apoptosis without apparent cell cycle arrest and effect on Rb phosphorylation. Investigation of multiple signaling pathways revealed that mitogen-induced phosphorylation and activation of AKT are inhibited in HIN-1-expressing cells. In addition, expression of constitutively activate AKT abrogates HIN-1-mediated growth arrest. Taken together, these studies provide further evidence that HIN-1 possesses tumor suppressor functions, and that these activities may be mediated through the AKT signaling pathway.

Published 3 November 2005 in Cancer Res, 65(21): 9659-69.
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