Figure 2.

The two states of K-Ras4A may contribute to different cancer types. We suggest that oncogenic K-Ras4A may mirror a K-Ras4B-like state in K-Ras4B-driven adenocarcinomas including colorectal, pancreatic, and lung cancers, whereas oncogenic K-Ras4A may reflect an N-Ras-like state in cancers where oncogenic N-Ras is frequent, such as melanoma and acute myeloid leukemia. The top panel provides estimated averages of K-Ras4A mRNA expression in different human cancer cell lines represented as a percentage of the total K-Ras expression, computed from the qPCR expression data in Fig. 1B of Tsai et al. (3). These unweighted averages were computed by measuring the percentages from the bar graphs in that figure, then summing the percentages from all cell lines of a given cancer type. The total for each cancer types was then divided by the number of cell lines reported for that cancer. This computation assumes that K-Ras4A expression is not dependent on whether the KRAS gene contains mutations. The bottom panel pie charts illustrate K-Ras4A expression in individual cell lines relative to all cell lines of that same tissue type, and suggest that significant variation exists even in the cancer types where K-Ras4A expression peaks. The percentages shown for each cell line were computed by taking the reported percentage expression for that cell line as a fraction of the sum of percentage expression levels for all cell lines of that cancer type. Here, the 4 colon and 6 melanoma cell lines reported in (3) are shown, with asterisks indicating those cell lines containing KRAS or NRAS mutations. We propose that the N-Ras-like state of K-Ras4A, in which it is palmitoylated and farnesylated, may contribute to its high expression levels in melanoma, whereas the K-Ras4B-like state of K-Ras4A, in which it is only farnesylated, may contribute to its high expression levels in colon cancer.