Association of activated proto-oncogenes ras and myc in colorectal carcinomas.
We have examined 60 colorectal carcinomas for activation of two proto-oncogenes, c-myc and c-Ki-ras. Over-expression of c-myc mRNA as determined by Northern analysis was found in 58% of cases (35/60). Activation of the c-Ki-ras gene by point mutations in codons 12 or 13 as determined by mismatch specific oligonucleotide hybridisation was found in 35% (21/60) of cases. There was a statistically significant association between activation of c-Ki-ras and over-expression of c-myc (P = 0.03), with 76% of tumours with an activated c-Ki-ras proto-oncogene showing over-expression of c-myc. The association was significant in left-sided colorectal tumours (P = 0.03) but not right-sided (P = 0.5). However, whereas only 59% of left side tumours showed at least one of the two changes (ras activation only, or myc activation only or both), 93% of right side tumours showed at least one of the changes (P = 0.01). Twenty-two percent of left side tumours showed both changes compared with 35% of right side tumours, although this result did not achieve significance (P = 0.2). These results suggest that in left-sided colorectal tumours ras and myc cooperate, as established in vitro, to produce neoplastic transformation while different pathway(s) are involved in right-sided tumours.
Smith
D R
DR
Department of Colorectal Surgery, Singapore General Hospital.
Elnatan
J
J
Myint
T
T
Goh
H S
HS
D001483:Base Sequence; D015152:Blotting, Northern; D015179:Colorectal Neoplasms / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D011905:Genes, ras; D006801:Humans; D008969:Molecular Sequence Data; D000090063:Proto-Oncogene Mas; D012334:RNA, Neoplasm / Q000032:analysis
D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012334:RNA, Neoplasm