[The role of cycline dependent kinase 4 in the malignant transformation induced by silica].
OBJECTIVE
To study the role of cycline dependent kinase 4 (CDK4) in the malignant transformation of human fetal lung diploid fibroblast cell (2BS) induced by silica.


METHODS
Recombination vectors with antisense pXJ41-CDK4 were constructed, and then were transfected into the malignant transformed cells induced by silica. In situ hybridization and immunohistochemistry were used to analyze the expression of CDK4. Cell growth curve, doubling time, cell cycle distribution and the growth capacities on soft agar were analyzed before and after antisense CDK4 RNA was transferred into malignant transformed cells induced by silica.


RESULTS
During the malignant transformation of 2BS cells induced by silica, CDK4 gene was overexpressed. Antisense pXJ41-CDK4 transduction suppressed CDK4 gene expression in the antisense pXJ41-CDK4 transfected cells. Antisense CDK4 RNA led to cell cycle arrest, resulting in lengthened G1 phase (the percentages of cells in the G1 phase increased from 45.1% to 58.0%), and eventually attenuated the proliferation of malignant transformed cells induced by silica. At the 8th day, the suppression rates decreased by 77.43%. The doubling time prolonged from 21.0 h to 42.7 h. The growth capacities on soft agar of cells transfected by antisense pXJ41-CDK4 were decreased.


CONCLUSIONS
CDK4 might play an important role in maintaining the transformed phenotype of the cancer cells.
Yan
Ke-xia
KX
Institute for Occupational Health and Poisoning Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China.
Liu
Bing-ci
BC
Shi
Xiang-lin
XL
Zhang
Xiang-min
XM
You
Bao-rong
BR
Xu
Ming
M
Kang
Ning
N
D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002478:Cells, Cultured; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000502:physiology*; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000166:cytology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D016372:RNA, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D012822:Silicon Dioxide / Q000633:toxicity*
D011518:Proto-Oncogene Proteins; D016372:RNA, Antisense; D012333:RNA, Messenger; D012822:Silicon Dioxide; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases