Different levels of v-Ha-ras p21 expression in primary keratinocytes transformed with Harvey sarcoma virus correlate with benign versus malignant behavior.

Primary mouse keratinocytes transformed with an activated ras oncogene transduced by helper-free Harvey sarcoma virus (HaSV) form predominantly benign tumors. In contrast, keratinocytes transformed with helper-associated HaSV form malignant tumors. We report here that this different tumorigenic behavior correlated with a much higher level of v-Ha-ras p21 protein in cells transformed with the helper-associated virus. The high level of v-ras expression in these cells was due to viral spread beyond the initial infection. The low level of v-ras p21 expression that resulted from single-hit infection with helper-free virus, together with the intrinsic heterogeneity of primary keratinocytes, explains, at least in part, the different tumorigenic behavior of keratinocytes transformed by the two types of viruses.