Multifunctional Role of Bcl-2 in Malignant Transformation and Tumorigenesis of Cr(VI)-Transformed Lung Cells

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)

Highly cited articles in environmental and occupational health, 1919-1960

Although numerous lists of "citation classics" have been compiled across a variety of scientific fields, few have included articles from environmental and occupational health (EOH). This investigation sought to identify and analyze the most highly cited articles ever published in the Journal of Industrial Hygiene (1919-1935), the Journal of Industrial Hygiene and Toxicology (1936-1949) the Archives of Industrial Hygiene and Occupational Medicine (1950), the American Medical Association (A.M.A.) Archives of Industrial Hygiene and Occupational Medicine (1950-1954), and the A.M.A. Archives of Industrial Health (1955-1960). Regularly cited topics included metal fume fever and various studies of beryllium, whereas the most highly cited article of all was a 1957 paper describing the control of heat casualties at military training centers. Interestingly, the most highly cited articles were not the oldest, and nor were they written as literature reviews. Overall, this Study suggests that although some citation patterns in EOH reflect those of other disciplines, the trend is not uniform and EOH itself appears to have some distinctive bibliometric characteristics