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Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 [W. E. A., J. L., M. P. W.]; Intramural Research Support Program, Science Applications International Corporation-Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702 [B. A. D.]; and Departments of Medicine and Zoology, Michigan State University, East Lansing, Michigan 48824 [S. T. Q., M. M. W.]
Prostate cancer has become epidemic, and environmental factors such as cadmium may be partly responsible. This study reports malignant transformation of the nontumorigenic human prostatic epithelial cell line RWPE-1 by in vitro cadmium exposure. The cadmium-transformed cells exhibited a loss of contact inhibition in vitro and rapidly formed highly invasive and occasionally metastatic adenocarcinomas upon inoculation into mice. The transformed cells also showed increased secretion of MMP-2 and MMP-9, a phenomenon observed in human prostate tumors and linked to aggressive behavior. Cadmium-induced malignant transformation of human prostate epithelial cells strongly fortifies the evidence for a potential role of cadmium in prostate cancer.
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