Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Dec 6;91(25):11874–11878. doi: 10.1073/pnas.91.25.11874

Stepwise immortalization and transformation of adult human prostate epithelial cells by a combination of HPV-18 and v-Ki-ras.

J S Rhim 1, M M Webber 1, D Bello 1, M S Lee 1, P Arnstein 1, L S Chen 1, G Jay 1
PMCID: PMC45338  PMID: 7991549

Abstract

Recent investigations have shown the presence of ras gene mutations and human papillomavirus (HPV) DNA in prostate carcinomas. In the present study, secondary adult human prostatic epithelial cells, upon transfection with a plasmid containing the entire HPV-18 genome, acquired an indefinite life-span in culture but did not undergo malignant conversion. Subsequent infection of these immortalized cells with the Kirsten murine sarcoma virus, which contains an activated Ki-ras oncogene, induced morphological transformation that led to the acquisition of neoplastic properties. These findings demonstrate the malignant transformation of adult human prostate epithelial cells in culture by a combination of viral oncogenes and the successive roles of HPV infection and Ki-ras activation in a multistep process responsible for prostate carcinogenesis.

Full text

PDF
11874

Images in this article

11875Image
on p.11875
11876Image
on p.11876
11876Image
on p.11876
11877Image
on p.11877

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anwar K., Nakakuki K., Shiraishi T., Naiki H., Yatani R., Inuzuka M. Presence of ras oncogene mutations and human papillomavirus DNA in human prostate carcinomas. Cancer Res. 1992 Nov 1;52(21):5991–5996. [PubMed] [Google Scholar]
  2. Barrasso R., De Brux J., Croissant O., Orth G. High prevalence of papillomavirus-associated penile intraepithelial neoplasia in sexual partners of women with cervical intraepithelial neoplasia. N Engl J Med. 1987 Oct 8;317(15):916–923. doi: 10.1056/NEJM198710083171502. [DOI] [PubMed] [Google Scholar]
  3. Boring C. C., Squires T. S., Tong T. Cancer statistics, 1993. CA Cancer J Clin. 1993 Jan-Feb;43(1):7–26. doi: 10.3322/canjclin.43.1.7. [DOI] [PubMed] [Google Scholar]
  4. Carter B. S., Epstein J. I., Isaacs W. B. ras gene mutations in human prostate cancer. Cancer Res. 1990 Nov 1;50(21):6830–6832. [PubMed] [Google Scholar]
  5. Carter H. B., Coffey D. S. The prostate: an increasing medical problem. Prostate. 1990;16(1):39–48. doi: 10.1002/pros.2990160105. [DOI] [PubMed] [Google Scholar]
  6. Coffey D. S. Prostate cancer. An overview of an increasing dilemma. Cancer. 1993 Feb 1;71(3 Suppl):880–886. doi: 10.1002/1097-0142(19930201)71:3+<880::aid-cncr2820711403>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
  7. Gumerlock P. H., Poonamallee U. R., Meyers F. J., deVere White R. W. Activated ras alleles in human carcinoma of the prostate are rare. Cancer Res. 1991 Mar 15;51(6):1632–1637. [PubMed] [Google Scholar]
  8. Isaacs J. T. Prostatic cancer: an overview. Cancer Metastasis Rev. 1993 Mar;12(1):1–2. doi: 10.1007/BF00689784. [DOI] [PubMed] [Google Scholar]
  9. Kaur P., McDougall J. K. Characterization of primary human keratinocytes transformed by human papillomavirus type 18. J Virol. 1988 Jun;62(6):1917–1924. doi: 10.1128/jvi.62.6.1917-1924.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Konishi N., Enomoto T., Buzard G., Ohshima M., Ward J. M., Rice J. M. K-ras activation and ras p21 expression in latent prostatic carcinoma in Japanese men. Cancer. 1992 May 1;69(9):2293–2299. doi: 10.1002/1097-0142(19920501)69:9<2293::aid-cncr2820690915>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
  11. Maloy W. L., Coligan J. E., Barra Y., Jay G. Detection of a secreted form of the murine H-2 class I antigen with an antibody against its predicted carboxyl terminus. Proc Natl Acad Sci U S A. 1984 Feb;81(4):1216–1220. doi: 10.1073/pnas.81.4.1216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. McNicol P. J., Dodd J. G. High prevalence of human papillomavirus in prostate tissues. J Urol. 1991 Apr;145(4):850–853. doi: 10.1016/s0022-5347(17)38476-8. [DOI] [PubMed] [Google Scholar]
  13. Rhim J. S., Fujita J., Arnstein P., Aaronson S. A. Neoplastic conversion of human keratinocytes by adenovirus 12-SV40 virus and chemical carcinogens. Science. 1986 Apr 18;232(4748):385–388. doi: 10.1126/science.2421406. [DOI] [PubMed] [Google Scholar]
  14. Rhim J. S., Jay G., Arnstein P., Price F. M., Sanford K. K., Aaronson S. A. Neoplastic transformation of human epidermal keratinocytes by AD12-SV40 and Kirsten sarcoma viruses. Science. 1985 Mar 8;227(4691):1250–1252. doi: 10.1126/science.2579430. [DOI] [PubMed] [Google Scholar]
  15. Rhim J. S., Park J. B., Jay G. Neoplastic transformation of human keratinocytes by polybrene-induced DNA-mediated transfer of an activated oncogene. Oncogene. 1989 Nov;4(11):1403–1409. [PubMed] [Google Scholar]
  16. Rijnders A. W., van der Korput J. A., van Steenbrugge G. J., Romijn J. C., Trapman J. Expression of cellular oncogenes in human prostatic carcinoma cell lines. Biochem Biophys Res Commun. 1985 Oct 30;132(2):548–554. doi: 10.1016/0006-291x(85)91168-4. [DOI] [PubMed] [Google Scholar]
  17. Sarkar F. H., Sakr W. A., Li Y. W., Sreepathi P., Crissman J. D. Detection of human papillomavirus (HPV) DNA in human prostatic tissues by polymerase chain reaction (PCR). Prostate. 1993;22(2):171–180. doi: 10.1002/pros.2990220210. [DOI] [PubMed] [Google Scholar]
  18. Sumiya H., Masai M., Akimoto S., Yatani R., Shimazaki J. Histochemical examination of expression of ras p21 protein and R 1881-binding protein in human prostatic cancers. Eur J Cancer. 1990;26(7):786–789. doi: 10.1016/0277-5379(90)90152-j. [DOI] [PubMed] [Google Scholar]
  19. Tanaka K., Appella E., Jay G. Developmental activation of the H-2K gene is correlated with an increase in DNA methylation. Cell. 1983 Dec;35(2 Pt 1):457–465. doi: 10.1016/0092-8674(83)90179-4. [DOI] [PubMed] [Google Scholar]
  20. Ullrich S. J., Sakaguchi K., Lees-Miller S. P., Fiscella M., Mercer W. E., Anderson C. W., Appella E. Phosphorylation at Ser-15 and Ser-392 in mutant p53 molecules from human tumors is altered compared to wild-type p53. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5954–5958. doi: 10.1073/pnas.90.13.5954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Viola M. V., Fromowitz F., Oravez S., Deb S., Finkel G., Lundy J., Hand P., Thor A., Schlom J. Expression of ras oncogene p21 in prostate cancer. N Engl J Med. 1986 Jan 16;314(3):133–137. doi: 10.1056/NEJM198601163140301. [DOI] [PubMed] [Google Scholar]
  22. Woodworth C. D., Bowden P. E., Doniger J., Pirisi L., Barnes W., Lancaster W. D., DiPaolo J. A. Characterization of normal human exocervical epithelial cells immortalized in vitro by papillomavirus types 16 and 18 DNA. Cancer Res. 1988 Aug 15;48(16):4620–4628. [PubMed] [Google Scholar]
  23. zur Hausen H. Human papillomaviruses in the pathogenesis of anogenital cancer. Virology. 1991 Sep;184(1):9–13. doi: 10.1016/0042-6822(91)90816-t. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES