The proposed studies will evaluate the potential for a unique nuclear structure, the perinucleolar compartment (PNC), to be used as an immunocytochemical marker in the diagnosis of cancer. The work will also purify and characterize the structural components of the PNC. The association between the PNC and carcinogenesis will also be analyzed. Preliminary studies have shown that he PNC is present in many human cancer cells lines, but is mostly absent from normal diploid cells. To test the correlation between the PNC and human cancer, PNC prevalence (the percentage of cells that contain a PNC) in a large number of cancer samples and their normal counterparts will be examined and compared. An antibody specifically recognizing a polypyrimidine binding protein (PTB), the only protein component identified in the PNC thus far, will be sued as a probe to detect the PNC. If a significant correlation between PNC prevalence and cancers of various clinical stages and pathological grades can be established, PNC prevalence may provide an additional marker in the diagnosis of the disease. In addition, the structural and functional characteristics of the PNC will be investigated using both molecular and cellular approaches. Additional components in the PNC will be identified, cloned, and the functional interactions among them will be analyzed. The role of the PNC in the process of carcinogenesis will also be examined. These proposed studies will inevitably further our understanding in the relationship between the PNC and cancers, as well as the structural and functional characteristics of the PNC. These work will also represent a link between the basic research and clinical applications.
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