Increased levels of phorbin, c-myc, and ornithine decarboxylase RNAs in human colon cancer.
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.
Guillem
J G
JG
Comprehensive Cancer Center, Columbia University, New York, New York.
Levy
M F
MF
Hsieh
L L
LL
Johnson
M D
MD
LoGerfo
P
P
Forde
K A
KA
Weinstein
I B
IB
D000199:Actins / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics*; D003424:Crohn Disease / Q000150:complications / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009955:Ornithine Decarboxylase / Q000235:genetics* / Q000378:metabolism; D010703:Phorbol Esters / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc; D012313:RNA / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000199:Actins; D014408:Biomarkers, Tumor; D010703:Phorbol Esters; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012313:RNA; D011493:Protein Kinase C; D009955:Ornithine Decarboxylase