K-ras and B-raf gene mutations are not associated with gastrin- and CCK2-receptor mRNA expression in human colorectal tumour tissues.
BACKGROUND
Colorectal cancer is a multistep process caused by genetic alterations in cell growth regulatory genes such as K-ras and B-raf. It has been assumed that mutations in the K-ras gene induce gastrin gene expression and that gastrin stimulates the growth of colorectal cancer in an autocrine fashion by coexpressing gastrin and cholecystokinin (CCK)2 receptors. The aim of this study was to examine a possible association of K-ras and B-raf gene mutations with gastrin and CCK2 receptor mRNA expression in human colon and rectum tumour biopsy specimens.


METHODS
K-ras and B-raf gene mutations as well as gastrin and CCK2 receptor mRNA expression in 50 colon and 46 rectum biopsies, respectively, were determined using molecular biology methods.


RESULTS
K-ras mutations occurred in 44% colon and 30% rectum and B-raf mutations in 16% colon and 4% rectum tumours, respectively. Gastrin mRNA was expressed in 64% colon and 61% rectum tumours, whereas CCK2 receptor mRNAs was expressed in 32% colon and 13% rectum tumours. K-ras or B-raf gene mutations and simultaneous gastrin mRNA expression was observed in 40% colon and 17% rectum tumours, respectively. Co-expression of gastrin and CCK2 receptor mRNA occurred in 20% colon and 9% rectal tumours.


CONCLUSIONS
The results do not support the hypothesis that K-ras and B-raf gene mutations have an impact on gastrin- and CCK-receptor mRNA expression in colorectal tumour tissues.
Monstein
H-J
HJ
University Hospital, Linköping University, University College of Health Sciences, Jönköping, Sweden. hanmo@ibk.liu.se
Fransén
K
K
Dimberg
J
J
Söderkvist
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005755:Gastrins / Q000096:biosynthesis / Q000235:genetics; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009367:Neoplasm Staging; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D043887:Receptor, Cholecystokinin B / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004273:DNA, Neoplasm; D005755:Gastrins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D043887:Receptor, Cholecystokinin B; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf