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Role of cyclinD1 and CDK4 in the carcinogenesis induced by silica.

Authors
Yan-KX; Liu-BC; Shi-XL; You-BR; Xu-M
Source
Biomed Environ Sci 2005 Oct; 18(5):286-296
NIOSHTIC No.
20028773
Abstract
To study the role of cyclinD1 and CDK4 in malignant transformation of human fetal lung diploid fibroblast cell line (2BS) induced by silica. Recombination vectors with sense and antisense pXJ41-cyclinDl 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. 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-cyclinDl 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. CyclinD1 and CDK4 play an important role in maintaining transformed phenotype of the cancer cells.
Keywords
Carcinogenesis; Carcinogenicity; Carcinogens; Silica-dusts; Silicates; Cell-transformation; Cancer; Free-radicals; Lung-cancer; Breast-cancer
CODEN
BESCE5
Publication Date
20051001
Document Type
Journal Article
Fiscal Year
2006
NTIS Accession No.
NTIS Price
Issue of Publication
5
ISSN
0895-3988
NIOSH Division
HELD
Priority Area
Research Tools and Approaches: Cancer Research Methods
Source Name
Biomedical and Environmental Sciences
State
WV
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