Inhibition of esophageal cancer proliferation by adenovirally mediated delivery of p16INK4.
We have been investigating the molecular basis of esophageal carcinogenesis in an attempt to develop gene therapy of established esophageal cancers and premalignant esophageal lesions. In this report we demonstrate the efficacy of adenovirally mediated p16 gene replacement in esophageal squamous cell cancers. Adenoviral p16 efficiently transduced epidermoid cancer cells containing p16 mutations, and expression of exogenous p16 in these cells correlated with G1 cell cycle arrest and profound growth inhibition. No effects were observed in esophageal adenocarcinoma cells due to extremely poor transduction of these cells by adenovirus. These results may have implications regarding the design of clinical trials using p16 gene replacement strategies for intervention in esophageal cancers.
Schrump
D S
DS
Department of Thoracic and Cardiovascular Surgery, University of Texas M.D. Anderson Cancer Center, Houston, USA.
Chen
G A
GA
Consuli
U
U
Jin
X
X
Roth
J A
JA
D000230:Adenocarcinoma / Q000378:metabolism / Q000628:therapy; D000256:Adenoviridae / Q000235:genetics*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000235:genetics*; D019938:Cyclin D1; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016213:Cyclins / Q000032:analysis / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000628:therapy*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000235:genetics; D015316:Genetic Therapy; D006801:Humans; D009374:Neoplasms, Experimental; D018307:Neoplasms, Squamous Cell / Q000378:metabolism / Q000628:therapy; D015513:Oncogene Proteins / Q000032:analysis / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000032:analysis / Q000378:metabolism; D014161:Transduction, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016213:Cyclins; D015513:Oncogene Proteins; D016160:Retinoblastoma Protein; D019938:Cyclin D1; D001616:beta-Galactosidase