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Title   DNA 로 유발된 쥐의 대장암에서 ras 암유전자의 점돌연변이 및 ras 유전자 p21 단백질의 발현 ( Point Mutation of c-K-ras Oncogene and p21 Protein Expression of v-K-ras & v-H-ras of Dimethylhydrazine-induced colon Cancer in Rats )
Publicationinfo   1992 Jan; 024(05): 619-630.
Key_word   ras oncogene, Point mutation, p21 protein
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Abstract   One of the important things in colon carcinogenesis has been known to be point mutation of ras oncogene and about 11 kinds of mutation on codon 12, 13 and 61 of k-ras or N-ras oncogene are reported by several investigators. In vertebrates, point mutation has been detected in chemical carcinogen induced cancers. Ras oncogene encoded protein product p21 has been knawn to regulate cell proliferation and differentiation by p21-GTP or GDT complex with point mutation. Investigators reported that p21 protein stimulated malignant transformation and its expression was changed by development and progress of cancers. To investigate the incidence of point mutation codon 12, 13 of c-K-ras oncogene in DMH-in-duced colon cancers and p21 protein products expression encoded by v-K-ras or v-H-ras oncogene according to exposure time of carcinogen and cell differentiation, authors divided 90 experimental animals into control(30) and experimental(60) groups. Each group was divided into three groups by sacrificing time after subcutaneous injection of 20 mg of DMH or iml of EDTA weekly for 20 weeks; group I(20 weeks), II(26 weeks) and III(32 weeks). Point mutations were detected by paired-PCR with mutation-specific primers and agarose gel electrophoresis in 23 colon cancer tissues and p21 protein product expressions were investigated by immunoperoxdase staining using mouse monoclonal IgG antibody against v-K-ras and v-H-ras endcoded p21 protein product as primary antibdoy and avidin-biotin complex. The results were obtained as follows: 1) The incidences of DMH-induced colon cancer were 30% in group I and II, 55% in group III. Overall 27 cases(23 animals) of colon cancers wre observed. But only one colon cancer and 23% of polyps were detected in control groups. Histopathologically 51.5% of well differntiated, 37% of moderately differentiated and I1.1% of poorly or mucinous adenocarcinomas were observed. 2) The indences of point mutation of 23 colon cancers were 34% of GAT, 17% of TGT, 17% of GTT mutation on codon 12 and 30% of GAC mutation with overall 78% of mutations. But no mutation was observed in normal colon tissues. 3) The expression of p2l protein products of v-K-ras in DMH induced colon cancers was 74% of positive which is consisted of 11% of A-type, 55% of C-type and 7% of S-type in 27 colon cancer tissues. C-type was gradually incresed from 17% of group I to 25% of group II and 92% of group III, while A-type was changed from 17% of group I to 25% of group II and 0% of group C. Simillary the expression of v-H-ras was 74% of positive which is consisted of 11% of A-type, 59 % of C-type and 4% of S-type in overalL C-type was incresed from 17% of group I to 37% of group II and 92% of group III. Positive expression was gradually increased from 33%(group I) to 62%(group II) and l00% (group II) in both v-K-ras and v-H-ras. 4) The positive p21 expressions for v-K-ras and v-H-ras were 69% and 77% in well differentiation and, 90% and 80% in moderately differentiated carcinomas. With above results, authors considered that point mutation of c-K-ras oncogene play an important role in DMH induced colon carcinogenesis. Expression of p21 protein product is increased by increasing DMH exposure time and differentiation which may be used in early detection and prediction of prognosis of colon cancers.
저 자   김용귀(Yong Gui Kim),박승만(Seung Man Park),장석균(Suk Kyun Chang),주상용(Sang Yong Choo)