Rab25: a suppressor of tumor formation in intestines?
- Date:
- February 9, 2010
- Source:
- Journal of Clinical Investigation
- Summary:
- Colorectal adenocarcinoma accounts for the majority of cases of colorectal cancer. A series of genetic mutations in the cells lining the colon (intestinal epithelial cells) is thought to be the cause of colorectal adenocarcinoma. By studying mouse models of colon cancer and tissue from individuals with colorectal adenocarcinoma, researchers have now identified RAB25 as one gene that might be involved in the formation of colorectal adenocarcinomas.
- Share:
Colorectal adenocarcinoma accounts for the majority of cases of colorectal cancer. A series of genetic mutations in the cells lining the colon (intestinal epithelial cells) is thought to be the cause of colorectal adenocarcinoma.
By studying mouse models of colon cancer and tissue from individuals with colorectal adenocarcinoma, James Goldenring and colleagues, at Vanderbilt University School of Medicine, Nashville, have now identified RAB25 as one gene that might be involved in the formation of colorectal adenocarcinomas.
Initial analysis indicated that expression of Rab25 was substantially decreased in human colon adenocarcinomas compared with normal colon and that lower Rab25 expression predicted shorter patient survival times.
To follow up on these data, which suggested that Rab25 functions as a tumor suppressor (that is, a protein that when expressed at lower than normal levels due to mutation of the gene responsible for its generation fails to prevent tumors forming) in intestinal epithelial cells, the authors analyzed Rab25-deficient mice. Although these animals showed no gross abnormalities, when they were crossed with mice that model a hereditary syndrome that predisposes to colon cancer (ApcMin/+ mice), the Rab25-deficient ApcMin/+ mice developed increased numbers of intestinal polyps and colonic tumors compared with parental ApcMin/+ mice.
Similar results were obtained in a second mouse model of colorectal adenocarcinoma, providing further confirmation of the probable tumor suppressor role of Rab25 in intestinal epithelial cells.
The research appears in the Journal of Clinical Investigation.
Story Source:
Materials provided by Journal of Clinical Investigation. Note: Content may be edited for style and length.
Journal Reference:
- Ki Taek Nam, Hyuk-Joon Lee, J. Joshua Smith, Lynne A. Lapierre, Vidya P. Kamath, Xi Chen, Bruce J. Aronow, Timothy J. Yeatman, Sheela G. Bhartur, Benjamin C. Calhoun, Brian Condie, Nancy R. Manley, R. Daniel Beauchamp, Robert J. Coffey, and James R. Goldenring. Loss of Rab25 promotes the development of intestinal neoplasia in mice and is associated with human colorectal adenocarcinomas. Journal of Clinical Investigation, 2010; DOI: 10.1172/JCI40728
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