H‐ras expression, genetic instability, and acquisition of metastatic ability by rat prostatic cancer cells following v‐H‐ras oncogene transfection

Tomohiko Ichikawa, Jack A. Schalken, Yayoi Ichikawa, Gary D. Steinberg, John T. Isaacs

Research output: Contribution to journalArticle

Abstract

To study the relationship between metastatic ability, mutated H‐ras expression, and genetic instability, a cloned, nonmetastatic rat prostatic cancer cell line (AT2.1) was transfected with the v‐H‐ras oncogene. The parental AT2.1 clone, 4 control transfectants (Neo/Only), and 9 v‐H‐ras transfectants (Neo/Ras) were characterized with regard to their H‐ras content by using Southern, Northern, and Western blot analysis and their biological behavior in vivo. Following s.c. inoculation in syngeneic rats, all transfectants produced tumors. All 4 (Neo/Only) transfectants like the parental untransfected cell were non‐metastatic. Six of 9 Neo/Ras transfectants were metastatic to the lungs and lymph nodes, while the other 3 Neo/Ras transfectants were not metastatic. There was no simple dose‐response relationship between the level of v‐H‐ras integration, mRNA or p21 protein expression, and the development of metastatic ability by the Neo/Ras transfectants. Cytogenetic analysis demonstrated that the frequency of additional structural and/or additional numerical chromosomal changes among the Neo/Ras transfectants was significantly higher than that in the Neo/Only transfectants (P <0.05). Loss of chromosome 10 was observed in all of the Neo/Ras transfectants, whereas that was observed in only one of the 4 Neo/Only transfectants (P <0.05). There were no specific chromosomal changes, however, which were statistically correlated with the development of metastases in the Neo/Ras transfectants. These results demonstrate that development of the metastatic ability in AT2.1 cells is not a single‐step reaction regulated by the level of H‐ras expression alone, but rather a complex process requiring additional events. One of the additional events appears to be an increase in genetic instability and cytogenetic changes following v‐H‐ras transfection.

Original languageEnglish (US)
Pages (from-to)163-172
Number of pages10
JournalThe Prostate
Volume18
Issue number2
DOIs
StatePublished - 1991

Keywords

  • H‐ras expression
  • genetic instability
  • prostatic cancer

ASJC Scopus subject areas

  • Oncology
  • Urology

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