Our previous work on
protein kinase C (PKC) and
colon cancer has shown altered levels of PKC activity in human colon
tumors, as well as activation of PKC by colon
tumor promoters such as
bile acids. To understand further the role of PKC in colon
carcinogenesis, we analyzed the expression of
phorbin, a gene induced by PKC activation, in a series of different stages of human colon
tumors. As shown by northern blot analyses of
poly (A)+ RNA, higher levels of phorbin
RNA were seen in 26 colon
tumor samples than in their adjacent normal colonic mucosa. There also appeared to be a correlation between the abundance of phorbin
RNA in the
tumors and the extent of invasion (
tumor-to-normal tissue phorbin
RNA ratio = 4.2, 8.0, and 11.9 for Dukes' A, B, and C, respectively). Phorbin
RNA was also abundant in a human
colon cancer line (HT29). We also examined the expression of other
mitogen-responsive genes (c-myc, ODC, and
beta-actin) in a set of 19 colon
tumor samples. All
tumors displayed significant (mean 3.8-fold) increases in the level of c-myc
RNA compared with their adjacent normal colonic mucosa. About 47% and 16% of these
tumor samples also showed increased levels of ODC (mean 3.1-fold) and
beta-actin (mean 1.6-fold)
RNA, respectively. The increased levels of c-myc, ODC, and
beta-actin RNA did not correlate with the extent of
tumor invasion. Taken together, these results demonstrate that human colon
tumors usually display increased levels of both phorbin and c-myc RNAs. The marked increases in phorbin
RNA suggest that this could serve as a useful
biomarker in studies on human
colon cancer.