Malignant transformation of human benign prostate epithelial cells by high linear energy transfer α-particles

  • Authors:
    • Hongzhen Li
    • Yongpeng Gu
    • Jun Miki
    • Bharati Hukku
    • David G. McLeod
    • Tom K. Hei
    • Johng S. Rhim
  • View Affiliations

  • Published online on: September 1, 2007     https://doi.org/10.3892/ijo.31.3.537
  • Pages: 537-544
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Abstract

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 α-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 α-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 α-particles. This model provides an opportunity to study the cellular and molecular alterations that occur in radiation carcinogenesis in human prostate cells.

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September 2007
Volume 31 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Li H, Gu Y, Miki J, Hukku B, McLeod DG, Hei TK and Rhim JS: Malignant transformation of human benign prostate epithelial cells by high linear energy transfer α-particles. Int J Oncol 31: 537-544, 2007.
APA
Li, H., Gu, Y., Miki, J., Hukku, B., McLeod, D.G., Hei, T.K., & Rhim, J.S. (2007). Malignant transformation of human benign prostate epithelial cells by high linear energy transfer α-particles. International Journal of Oncology, 31, 537-544. https://doi.org/10.3892/ijo.31.3.537
MLA
Li, H., Gu, Y., Miki, J., Hukku, B., McLeod, D. G., Hei, T. K., Rhim, J. S."Malignant transformation of human benign prostate epithelial cells by high linear energy transfer α-particles". International Journal of Oncology 31.3 (2007): 537-544.
Chicago
Li, H., Gu, Y., Miki, J., Hukku, B., McLeod, D. G., Hei, T. K., Rhim, J. S."Malignant transformation of human benign prostate epithelial cells by high linear energy transfer α-particles". International Journal of Oncology 31, no. 3 (2007): 537-544. https://doi.org/10.3892/ijo.31.3.537