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Cancer Specific Proliferating Cell Nuclear Antigen as a Novel Diagnostic Marker for the Detection of Breast Cancer

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Annual Summary rept. 1 Oct 2002-30 Sep 2003

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Our laboratory has demonstrated the presence of different isoforms of proliferating cell nuclear antigen PCNA that display both acidic and basic isoelectric points pI . Analysis of PCNA by two- dimensional polyacrlamide gel electrophoresis 2D PAGE from both malignant and non-malignant breast cells and tissues established the exclusive presence of the acidic form of PCNA in malignant cells which is now referred to as the cancer-specific form of PCNA or csPCNA. Additionally, a basic form of PCNA was also observed in the malignant cells, but this isoform was the only isoform found in non-malignant cells and tissues. Testing of numerous other malignant and non-malignant breast cells suggested that the csPCNA would be an excellent prognostic indictor of breast cancer. Further investigation confirmed that a 29 amino acid fragment derived from the PCNA binding domain of the XPG protein interacted with csPCNA and not the basic PCNA isoform. This led us to believe that the xPG peptide would be a specific and sensitive probe that would enable us to identify csPCNA in different tissue and serum samples. It is therefore our goal in this research to develop an enzyme linked immunosorbent assay ELISA that utilizes the 29 amino acid fragment of XPG to detect the presence of csPCNA in cells, tissues, and sera. Additionally, we plan on using the XPG peptide for immunocytochemical IHC staining allowing us to look for csPCNA in tissues of patients with breast cancer and uncertain malignant diagnosis. Following development of these assays, we will then screen our breast tissue and serum repositories, which we have been generating, and correlate our finding with other prognostic factors such as BECAl and 2, p53, p2exp kip, and estrogen receptor status and thus validate the usefulness of csPCNA as an earl diagnostic marker in breast cancer. 14 SUBJECT TERMS 15. NUMBER OF PAGES

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  • Anatomy and Physiology
  • Medicine and Medical Research

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