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Multifunctional role of Bcl-2 in malignant transformation and tumorigenesis of Cr(VI)-transformed lung cells.

Authors
Medan-D; Luanpitpong-S; Azad-N; Wang-L; Jiang-B-H; Davis-ME; Barnett-JB; Guo-L; Rojanasakul-Y
Source
PLoS One 2012 May; 7(5):e37045
NIOSHTIC No.
20040854
Abstract
B-cell lymphoma-2 (Bcl-2) is an antiapoptotic protein known to be important in the regulation of apoptosis in various cell types. However, its role in malignant transformation and tumorigenesis of human lung cells is not well understood. We previously reported that chronic exposure of human lung epithelial cells to the carcinogenic hexavalent chromium Cr(VI) caused malignant transformation and Bcl-2 upregulation; however, the role of Bcl-2 in the transformation is unclear. Using a gene silencing approach, we showed that Bcl-2 plays an important role in the malignant properties of Cr(VI)-transformed cells. Downregulation of Bcl-2 inhibited the invasive and proliferative properties of the cells as well as their colony forming and angiogenic activities, which are upregulated in the transformed cells as compared to control cells. Furthermore, animal studies showed the inhibitory effect of Bcl-2 knockdown on the tumorigenesis of Cr(VI)-transformed cells. The role of Bcl-2 in malignant transformation and tumorigenesis was confirmed by gene silencing experiments using human lung carcinoma NCI-H460 cells. These cells exhibited aggressive malignant phenotypes similar to those of Cr(VI)-transformed cells. Knockdown of Bcl-2 in the H460 cells inhibited malignant and tumorigenic properties of the cells, indicating the general role of Bcl-2 in human lung tumorigenesis. Ingenuity Pathways Analysis (IPA) revealed potential effectors of Bcl-2 in tumorigenesis regulation. Additionally, using IPA together with ectopic expression of p53, we show p53 as an upstream regulator of Bcl-2 in Cr(VI)-transformed cells. Together, our results indicate the novel and multifunctional role of Bcl-2 in malignant transformation and tumorigenesis of human lung epithelial cells chronically exposed to Cr(VI).
Keywords
Cell-function; Cell-biology; Cellular-function; Cellular-structures; Lung; Lung-cells; Carcinogens; Chromium-compounds; Genes; Animal-studies; Animals; Malignancy; Tumorigenesis
CODEN
POLNCL
Publication Date
20120501
Document Type
Journal Article
Email Address
yrojan@hsc.wvu.edu
Fiscal Year
2012
NTIS Accession No.
NTIS Price
Identifying No.
B06202012
Issue of Publication
5
ISSN
1932-6203
NIOSH Division
HELD
Source Name
Public Library of Science One
State
WV
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