Expression of proliferating cell nuclear antigen in gastrointestinal tract lesions and its relationship to bcl-2 expression.
We report the relationship between proliferation as measured by the expression of proliferating cell nuclear antigen (PCNA) and the proto-oncogene bcl-2 in inflammatory and neoplastic lesions of the gastrointestinal tract and associated normal tissues. We found that (1) PCNA and bcl-2 are coexpressed in the stem cell-regenerative compartments of normal tissues but are not coexpressed in carcinomas or adjacent histologically normal epithelium, (2) there is marked heterogeneity of PCNA and bcl-2 expression in neoplastic lesions of the gastrointestinal tract, and (3) overexpression of PCNA is frequently seen in histologically inactive ulcerative colitis. We postulate (1) increased bcl-2 expression in epithelium adjacent to tumors represents an inherent change in the morphologically normal epithelium because it occurs without the corresponding high proliferative state seen in the normal crypt-regenerative compartment, (2) heterogeneity may provide a mechanistic explanation for chemotherapeutic resistance in tumors since cells having high bcl-2 but low proliferative activity would have prolonged survival and might show resistance to chemotherapeutic agents, and (3) the increased proliferative state in histologically inactive ulcerative colitis may provide a partial explanation for the increased risk of colon carcinomas in these patients.
Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia 19104, USA.
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K
Bell
M P
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Bronner
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Pasha
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Furth
D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary; D001659:Biliary Tract / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003106:Colon / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D005767:Gastrointestinal Diseases / Q000378:metabolism*; D005770:Gastrointestinal Neoplasms / Q000378:metabolism; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism; D008113:Liver Neoplasms / Q000556:secondary; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D010179:Pancreas / Q000378:metabolism; D011230:Precancerous Conditions / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis* / Q000235:genetics; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics
C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D018809:Proliferating Cell Nuclear Antigen; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2