Faculty Publications

Yeung AT, Patel BB, Li XM, Seeholzer SH, Coudry RA, Cooper HS, Bellacosa A, Boman BM, Zhang T, Litwin S, Ross EA, Conrad P, Crowell JA, Kopelovich L, Knudson A

One-hit effects in cancer: Altered proteome of morphologically normal colon crypts in Familial Adenomatous Polyposis

Cancer Res. 2008 Sep;68(18):7579-86.

Abstract We studied patients with Familial Adenomatous Polyposis (FAP) because they are virtually certain to develop colon cancer, and because much is known about the causative APC gene. We hypothesized that the inherited heterozygous mutation itself leads to changes in the proteome of morphologically normal crypts and the proteins that changed may represent targets for preventive and therapeutic agents. We determined the differential protein expression of morphologically normal colon crypts of FAP patients versus those of individuals without the mutation, using two-dimensional gel electrophoresis, mass spectrometry, and validation by two-dimensional gel Western blotting. Approximately 13% of 1,695 identified proteins were abnormally expressed in the morphologically normal crypts of APC mutation carriers, indicating that a colon crypt cell under the one-hit state is already abnormal. Many of the expression changes affect pathways consistent with the function of the APC protein, in!