Increased apoptosis in metastatic human colonic adenocarcinomas.
Recent work suggests that apoptosis is disrupted during the progression of many solid tumors. Isogenic metastatic colon adenocarcinoma cells displayed significantly higher levels of staurosporine-induced apoptosis compared to their nonmetastatic counterparts in vitro. In addition, analysis of 15 matched primary tumors and liver metastases demonstrated that the levels of apoptosis were significantly higher in the metastases, and this increased cell death was associated with significantly lower levels of Bcl-2 protein expression. Our data demonstrate that the molecular events associated with acquisition of the metastatic phenotype sensitize colon cancer cells to some pro-apoptotic stimuli.
Termuhlen
Paula M
PM
Departments of Cancer Biology, Surgical Oncology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Sweeney-Gotsch
Bridget M
BM
Berman
Russell S
RS
Ellis
Lee M
LM
Bucana
Corazon
C
Shen
Yu
Y
Cleary
Karen R
KR
McConkey
David J
DJ
D000230:Adenocarcinoma / Q000473:pathology* / Q000556:secondary; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins; D003110:Colonic Neoplasms / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D019254:Genes, bcl-2; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary; D008562:Membrane Glycoproteins / Q000494:pharmacology; D009362:Neoplasm Metastasis / Q000473:pathology*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012189:Retrospective Studies; D019311:Staurosporine / Q000494:pharmacology; D053221:TNF-Related Apoptosis-Inducing Ligand; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019014:fas Receptor / Q000276:immunology / Q000502:physiology
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D019311:Staurosporine