[Effects of p21WAF1/CIP1 gene introduction on a human lung cancer cell line with p53 mutation].
OBJECTIVE
To study the effects of p21WAF1/CIP1 gene expression on the biological hehavior of cancer cells with p53 gene mutation.


METHODS
Expression of p21 vehicle was constructed and introduced into a human lung cancer cell ling PG with p53 gene mutation, the morphological and growth characteristics of the transfectant were then analysed. The CDK4 and PCNA levels were evaluated and the response to genotoxic agents were observed.


RESULTS
The PG cells with mutant p53 were transfected with ectopic p21 gene which resulted in overexpression of p21 (6-fold of the control). The transfectants presented decreased nuclear irregularity and thinner membrane in nuclear atypia, with delayed growth rate and contact growth inhibition. The transfectant also displayed high serum requirement in culture and increased anchorage dependence. Both levels of CDK4 and PCNA were decreased. However, the cisplatin induced cell apoptosis was delayed.


CONCLUSIONS
Expression of p21WAF1/CIP1 gene was effective in cancer suppression even in p53 gene mutation. This may have been achieved through lowering of CDK4 or PCNA levels and not involving the apoptosis mechanism. Activation of p21WAF1/CIP1 gene may be considered a bypass for restoration of p53 gene function in cancer cells with p53 gene mutation.
Zhuo
Y
Y
Department of Pathology, Beijing Medical University, Beijing 100083.
Zhang
B
B
Li
T
T
Wang
H
H
Li
S
S
Hou
L
L
Wu
B
B
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D003470:Culture Media / Q000494:pharmacology; D051358:Cyclin-Dependent Kinase 4; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008854:Microscopy, Electron; D009154:Mutation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D003470:Culture Media; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D002945:Cisplatin