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.