Ano1 as a regulator of proliferation

American Journal of Physiology - Gastrointestinal and Liver Physiology - Tập 301 Số 6 - Trang G1044-G1051 - 2011
Jennifer E. Stanich1, Simon J. Gibbons1, Seth T. Eisenman1, Michael R. Bardsley1, Jason R. Rock2, Brian D. Harfe3, Tamás Ördög1, Gianrico Farrugia4,1
1Enteric Neuroscience Program, Department of Physiology and Biomedical Engineering and
2Department of Cell Biology, Duke University Medical Center, Durham, North Carolina.
3Department of Molecular Genetics and Microbiology, The Genetics Institute, University of Florida, Gainesville, Florida
4Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota

Tóm tắt

Ano1 is a recently discovered Ca2+-activated Cl− channel expressed on interstitial cells of Cajal (ICC) that has been implicated in slow-wave activity in the gut. However, Ano1 is expressed on all classes of ICC, even those that do not contribute to generation of the slow wave, suggesting that Ano1 may have an alternate function in these cells. Ano1 is also highly expressed in gastrointestinal stromal tumors. Mice lacking Ano1 had fewer proliferating ICC in whole mount preparations and in culture, raising the possibility that Ano1 is involved in proliferation. Cl− channel blockers decreased proliferation in cells expressing Ano1, including primary cultures of ICC and in the pancreatic cancer-derived cell line, CFPAC-1. Cl− channel blockers had a reduced effect on Ano1(−/−) cultures, confirming that the blockers are acting on Ano1. Ki67 immunoreactivity, 5-ethynyl-2′-deoxyuridine incorporation, and cell-cycle analysis of cells grown in low-Cl− media showed fewer proliferating cells than in cultures grown in regular medium. We confirmed that mice lacking Ano1 had less phosphorylated retinoblastoma protein compared with controls. These data led us to conclude that Ano1 regulates proliferation at the G1/S transition of the cell cycle and may play a role in tumorigenesis.

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American Journal of Physiology - Gastrointestinal and Liver Physiology

Tập 301 Số 6

G1044-G1051

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