Role of cyclinD1 and CDK4 in the carcinogenesis induced by silica.
OBJECTIVE
To study the role of cyclinD1 and CDK4 in malignant transformation of human fetal lung diploid fibroblast cell line (2BS) induced by silica.


METHODS
Recombination vectors with sense and antisense pXJ41-cyclinD1 and pXJ41-CDK4 were constructed, and then transfected into the malignant transformed cells induced by silica, respectively. At the same time, pXJ41-neo was used as the control.


RESULTS
During the progress of the malignant transformation of 2BS cells induced by silica, cyclinD1 and CDK4 were overexpressed. Antisense RNA suppressed cyclinD1 and CDK4 gene expression in the antisense pXJ41-cyclinD1 and pXJ41-CDK4 transfected cells. Antisense RNA led to cell cycle arrest, resulting in lengthened G1 phase (the percentages of cells in the G1 phase changed from 45.1% to 52.7% and 58.0% for cyclinD1 and CDK4 transfected cells, respectively), and eventually attenuated the increase of the proliferation of malignant transformed cells induced by silica. Compared with malignant transformed cells induced by silica, cells transfected with antisense pXJ41-cyclinD1 and pXJ41-CDK4 showed obviously reduced growth rates. On the 8th day, the suppression rates were 58.69 and 77.43% (the growth rate of malignant transformed cells induced by silica was 100%), doubling time changed from 21.0 h to 31.4 h and 21.0 h to 42.7 h, respectively, the growth capacities on soft agar of cells transfected by antisense pXJ41-cyclinD1 and pXJ41-CDK4 decreased obviously.


CONCLUSIONS
CyclinD1 and CDK4 play an important role in maintaining transformed phenotype of the cancer cells.
Yan
Ke-Xia
KX
National Institute of Occupational Health and Poisons Control, Chinese Center for Disease Control and Prevention, 29 Nan Wei Road, Beijing 100050, China.
Liu
Bing-Ci
BC
Shi
Xiang-Lin
XL
You
Bao-Rong
BR
Xu
Ming
M
D002274:Carcinogens, Environmental / Q000633:toxicity*; D002460:Cell Line; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D010957:Plasmids; D016372:RNA, Antisense / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012822:Silicon Dioxide / Q000633:toxicity*
D002274:Carcinogens, Environmental; D016372:RNA, Antisense; D012333:RNA, Messenger; D019938:Cyclin D1; D012822:Silicon Dioxide; D051358:Cyclin-Dependent Kinase 4