BCL2 expression correlates with metastatic potential in pancreatic cancer cell lines.
BACKGROUND
Programmed cell death (termed apoptosis) regulates normal tissue homeostasis. Loss of local paracrine signals and intercellular adhesion molecules are potent inducers of apoptosis and thereby eliminate normal cells that may have escaped beyond the confines of the local organ environment. Dysregulation in the expression of the BCL2 gene family, the prototypic regulators of apoptosis, is a common occurrence in cancer and imparts resistance to standard triggers of apoptosis. Therefore, the authors sought to examine whether abnormal BCL2 gene family expression correlated with resistance 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 metastatic potential. Stable transfectants were generated that overexpress BCL2. These transfectants were then analyzed for differences in metastasis formation in athymic mice.


RESULTS
Among the isogenic panels of pancreatic cancer cell lines, BCL2 expression levels correlated with metastatic potential. Highly metastatic variants of each family of cell lines were more resistant to induction of apoptosis. 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 carcinoma.
Bold
R J
RJ
Department of Surgery, University of California Davis, Sacramento, California, USA. richard.bold@ucdmc.ucdavis.edu
Virudachalam
S
S
McConkey
D J
DJ
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D008113:Liver Neoplasms / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D014407:Tumor Cells, Cultured
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C090468:TP53BP2 protein, human