BCL2 expression correlates with metastatic potential in pancreatic cancer cell lines

BACKGROUND. Programmed cell death (termed apoptosis) regulates normal tissu e homeostasis. Loss of local paracrine signals and intercellular adhesion m olecules are potent inducers of apoptosis and thereby eliminate normal cell s that may have escaped beyond the confines of the local organ environment. Dysregulation in the expression of the BCL2 gene family, the prototypic re gulators of apoptosis, is a common occurrence in cancer and imparts resista nce to standard triggers of apoptosis. Therefore, the authors sought to exa mine whether abnormal BCL2 gene family expression correlated with resistanc e to apoptosis and increased metastatic potential in pancreatic carcinoma. METHODS. The authors examined BCL2 expression and apoptotic sensitivity in three panels of human pancreatic cancer cell lines that possess varying met astatic potential, Stable transfectants were generated that overexpress BCL 2. These transfectants were then analyzed for differences in metastasis for mation in athymic mice. RESULTS. Among the isogenic panels of pancreatic cancer cell lines, BCL2 ex pression levels correlated with metastatic potential. Highly metastatic var iants of each family of cell lines were more resistant to induction of apop tosis. Finally, using the BCL2 transfectant in a xenograft model, elevated BCL2 expression led to a higher incidence of metastases. CONCLUSIONS. The authors conclude that increased BCL2 expression correlates with apoptotic resistance and metastatic potential; dysregulation of BCL2 expression may be involved in the metastatic progression of pancreatic carc inoma.(C) 2001 American Cancer Society.