Cadmium-induced neoplastic transformation of human prostate epithelial cells.
Cadmium is a ubiquitous environmental human carcinogen. Epidemiological and animal studies have suggested its carcinogenic potential on the prostate. In the present study, non-tumorigenic human prostate epithelial cells (pRNS-1-1) immortalized by simian papovavirus (SV40) were transformed after repeated exposures to cadmium. Such transformants showed morphological alterations, anchorage-independent growth in soft agar, and formed tumors when transplanted into SCID mice. The tumors were characterized histologically as poorly-differentiated adenocarcinomas, expressing prostate-specific antigen (PSA), androgen receptor (AR), prostate stem cell antigen (PSCA), NKX3.1 and cytokeratin 8 (CK8). These findings provide evidence of malignant transformation of human prostate epithelial cells exposed to this environmentally important chemical.
Nakamura
Keiichiro
K
Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Yasunaga
Yutaka
Y
Ko
Daejin
D
Xu
Linda L
LL
Moul
Judd W
JW
Peehl
Donna M
DM
Srivastava
Shiv
S
Rhim
Johng S
JS
D000230:Adenocarcinoma / Q000473:pathology; D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D007621:Karyotyping; D007633:Keratins / Q000096:biosynthesis; D008297:Male; D051379:Mice; D016513:Mice, SCID; D017430:Prostate-Specific Antigen / Q000096:biosynthesis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011944:Receptors, Androgen / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013539:Simian virus 40 / Q000235:genetics; D013997:Time Factors; D014407:Tumor Cells, Cultured
D011944:Receptors, Androgen; D002104:Cadmium; D007633:Keratins; D017430:Prostate-Specific Antigen