Abstract 4792: Immune response to a fetal oncoprotein p90/CIP2A in lung cancer

Abstract

Abstract During a previous study which identified a cytoplasmic RNA-binding protein p62/IMP2 binding to and regulating the expression of IGF-II mRNA, it was noted that autoantibody against an antigen of approximately 90 kDa (p90) was detected with similar frequency in hepatocellular carcinoma (HCC). Full-length cDNA encoding p90 was successfully isolated from a T24 expression library and comprised a sequence coding for a protein of 905 amino acids with predicted molecular mass of 102kDa. Preliminary data showed that anti-p90 was present in 21/160 (13.1%) in HCC, 3/91 (3.3%) in gastric cancer and 1/20 (5.0%) in esophageal cancer. Gastric cancer tissue confirmed cytoplasmic expression of p90. Of interesting finding is that recently a research group showed that p90 could be co-purified with the A subunit of protein phosphatase 2A (PP2A). They showed that p90 was an inhibitor of the tumor suppressor function of PP2A and that this was related to p90 binding c-myc and inhibiting dephosphorylation of S62 by PP2A. They proposed renaming p90, the cancerous inhibitor of PP2A (CIP2A). CIP2A was shown to be overexpressed in low-passaged cell lines from head and neck squamous cell carcinoma. In order to address the possibility whether the p90/CIP2A might be a tumor-associated antigen (TAA) and useful as a biomarker in lung cancer, the full-length recombinant p90/CIP2A protein was used as the antigen in enzyme-linked immunoassay (ELISA) and western blot for the detection of autoantibodies in 105 sera from lung cancer patients. Frequency of autoantibodies to p90/CIP2A was 25.7% (27/105) in lung cancer, showing a significant difference compared to normal individuals (4.9%, 4/82). Positive sera in ELISA were also confirmed by western blot. In further study, the expression of p90/CIP2A in multiple lung cancer tissues (lung cancer tissue array) was evaluated by immunohistochemistry (IHC). Of the 72 lung cancer tissue specimens examined, increased expression of p90/CIP2A was observed in 61 (84.7%) specimens, which is significant higher than in normal lung tissues (14.3%, 9/63). Using confocal microscopy, we were able to confirm our previous finding that p90/CIP2A was predominately localized in the cytoplasm, which was consistent with our IHC data. Depletion of p90/CIP2A via shRNA in A549 lung cancer cell line resulted in the decreased cell proliferation, foci formation and inhibition of anchorage-independent growth. The examination of the dynamic expression of p90/CIP2A during mouse development shows that this protein is mainly expressed during embryo development, and becomes silent after birth. Together with antibodies against other well-validated TAAs such as p53, p62/IMP2 and so on, autoantibody to p90/CIP2A may provide a potential novel marker for lung cancer detection. In addition, our data also support the working hypothesis that autoantibody production in cancer may be directly linked to aberrant expression of proteins involved in tumorigenesis pathways. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4792.