Cloning and characterization of a novel 90 kDa 'companion' auto-antigen of p62 overexpressed in cancer.
Recently our laboratory identified a cytoplasmic RNA-binding protein p62 which binds to and regulates the expression of IGF II mRNA. p62 was initially shown to be recognized by auto-antibodies in hepatocellular carcinoma (HCC) but now anti-p62 has been described in diverse malignancies. p62 is uniformly expressed in fetal liver and prominently in 33% of HCC nodules, but not detectable in adult liver or normal tissue adjacent to HCC nodules. In this study, a 90 kDa protein (p90), auto-antibodies to which were found associated with anti-p62 responses in the same HCC patient group, was identified by cDNA expression cloning. Indirect immunofluorescence showed that, like p62, p90 localized to the cytoplasm in cultured cells and mouse fetal, but not adult liver. Among 11 human gastric cancer tissues examined, p90 was overexpressed in six (55%). Together with other cancer associated auto-antibodies such as anti-p53, anti-p62, anti-Koc, and anti-CENP-F, auto-antibodies to p90 represent a new marker for tumors such as HCC and gastric cancer. Our data support the working hypothesis that auto-antibody production in cancer may be directly linked to aberrant auto-antigen expression.
WM Keck Autoimmune Disease Center and DNA Core Laboratory for Structural Analysis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California, CA 92037, USA.
Linda
L
Soo Hoo
Jianying Y
JY
Zhang
Edward K L
EK
Chan
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology; D001324:Autoantigens / Q000096:biosynthesis / Q000235:genetics*; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000276:immunology; D003001:Cloning, Molecular; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000276:immunology
D000951:Antigens, Neoplasm; D001324:Autoantigens; C118585:P62 protein, human; D016601:RNA-Binding Proteins