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

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