Raf-1 kinase, epidermal growth factor receptors, and mutant Ras proteins in colonic carcinomas.
Epidermal growth factor receptors (EGFR) and ras mutations are known to play a significant role in controlling cell growth and tumor promotion. Both of them transmit mitogenic signals to the nucleus by activation of Raf-1 kinase. In this study, the expression of EGFR and mutant Ras proteins, and, for the first time, the expression, phosphorylation and kinase activity of Raf-1 kinase have been determined in paired samples of colorectal cancer and mucosa. The tumor and mucosa samples did not differ significantly with regard to Raf-1 kinase content and activity. A major difference between tumors and mucosa was found, however, in the phosphorylation of Raf-1. Most of the mucosa samples (13/20), but only 1/20 of the cancer samples, contained hyperphosphorylated Raf-1. EGFR were significantly (p = 0.0025) decreased in the tumors. The decreased phosphorylation of Raf-1 in colonic carcinomas could be the result of activation of Raf-1 phosphatases or inactivation of kinases phosphorylating Raf-1. New forms of treatment based on EGFR overexpression do not seem to be suitable for the majority of colonic cancers.
Eggstein
S
S
Chirurgische Universitätsklinik Freiburg, Abteilung Allgemeine Chirurgie mit Poliklinik, Germany.
Manthey
G
G
Hirsch
T
T
Baas
F
F
Specht
B U
BU
Farthmann
E H
EH
D000230:Adenocarcinoma / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000032:analysis*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D017354:Point Mutation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf; D018631:ras Proteins / Q000032:analysis* / Q000235:genetics
D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D018631:ras Proteins