Comparative Assessment Expression of the Inhibitor of Growth 1 Gene ( ING1 ) in Normal and Neoplastic Tissues

Abstract

Studies have indicated that the tumor suppressor p33 ^ING1b (13q33-34) interact with p53. Moreover, the association of functional protein forms of each member of the p33 ^ING1b /p53 complex is essential for optimum activity of p53. The present report describes the sequencing of cDNAs corresponding to the p33 ^ING1b mRNAs in a series of normal and tumor cell lines, and the production of monoclonal antibodies (MAbs) reactive with p33 ^ING1b . These antibodies were subsequently used to analyze p33 ^ING1b expression in normal and tumor cell lines and tissues. No evidence of mutation of p33 ^ING1b was found in any of the 15 tumor cell lines cDNAs studied. Our investigation of a wide range of normal tissues have shown that expression of the nuclear epitope is highly ubiquitous, whereas expression of the cytoplasmic form could be detected in only 50% of tissues studied. Considering neoplastic tissues, loss of nuclear p33 ^ING1b was observed in melanoma, seminoma, papillary thyroid carcinoma, ductal breast carcinoma, and acute lymphoblastic leukemia. As with normal tissue, cytoplasmic p33 ^ING1b was more restricted, being observed in around 30% of neoplastic tissues, but in melanoma, papillary thyroid carcinoma, ductal breast carcinoma, there was increased detection of cytoplasmic p33 ^ING1b associated with concomitant loss of nuclear expression. These results may suggest that at least in some tumors, loss of effective p33 ^ING1b function may be achieved by translocation to the cytoplasm or failure of nuclear localization.