Malignant transformation of human benign prostate epithelial cells by high linear energy transfer alpha-particles.
Although epidemiological studies have suggested a positive correlation between environmental radon exposure and prostate cancer, the mechanism involved is not clear. In the present study, we examined the oncogenic transforming potency of alpha-particles using non-tumorigenic, telomerase-immortalized human benign prostate epithelial cells. We report the malignant transformation of human benign prostate epithelial cells after a single exposure to 0.6 Gy dose of alpha-particles. Transformed cells showed anchorage-independent growth in soft agar and induced progressively growing tumors when transplanted into SCID mice. The tumors were characterized histologically as poorly differentiated adenocarcinomas. The cell line derived from tumor (SCID 5015), like the unirradiated cells, expressed cytokeratin 5, 8 and 18, NKX3.1 and AMACR. The malignant cells showed increased secretion of MMP2. Stepwise chromosomal changes in the progression to tumorigenicity were observed. Chromosome abnormalities were identified in both irradiated and tumorigenic cells relative to the non-irradiated control cells. Prominent changes in chromosomes 6, 11 and 16, as well as mutations and deletions of the p53 gene were observed in the tumor outgrowth and tumor cells. These findings provide the first evidence of malignant transformation of human benign prostate epithelial cells exposed to a single dose of alpha-particles. This model provides an opportunity to study the cellular and molecular alterations that occur in radiation carcinogenesis in human prostate cells.
Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Hongzhen
H
Li
Yongpeng
Y
Gu
Jun
J
Miki
Bharati
B
Hukku
David G
DG
McLeod
Tom K
TK
Hei
Johng S
JS
Rhim
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000209:etiology* / Q000473:pathology; D000512:Alpha Particles; D000818:Animals; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D002869:Chromosome Aberrations; D006801:Humans; D018499:Linear Energy Transfer; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D011467:Prostate / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000209:etiology* / Q000473:pathology