Comparative assessment expression of the inhibitor of growth 1 gene (ING1) in normal and neoplastic tissues.
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.
Nouman
Ghassan S
GS
Department of Pathology, Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4PH, UK.
Angus
Brian
B
Lunec
John
J
Crosier
Steve
S
Lodge
Andrew
A
Anderson
John J
JJ
D000236:Adenoma / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism; D018797:Cell Cycle Proteins; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins; D016147:Genes, Tumor Suppressor; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D008545:Melanoma / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011485:Protein Binding; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013936:Thymidine / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D000911:Antibodies, Monoclonal; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D004247:DNA; D013936:Thymidine