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KMID : 0350519920450020503
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Journal of Catholic Medical College
1992 Volume.45 No. 2 p.503 ~ p.515
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Point Mutation of ras Oncogene and P21 Protein Expression of Dimethylhydrazine-induced Colon Cancer in Rats
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Abstract
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One of the important things in colon carcincgenesis 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 carciongen induced cancers.
Ras oncogene encoded protein product p21 has been known to regulate cell proliferation and differentiation by p21-GTP complex with point mutation. Investigators reported that p21 protein stimulated maligant transformation and its expression was
changed
by development and progress of cancers.
To investigate the incidence of point mutation on codon 12, 13 of c-K-ras oncogene in DMH-induced colon cacers and p21 protein products expression enceded 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 20mg of DMH or 1ml of EDTA weekly for 20 weeks; group I (20weeks),
II(26
weeks) and III(32 weeks).
Point mutatios were detected by paired-PCR with mutation-specific primers and agarose gel electrophoresis in 23 colon cacer tissues and p21 protein product expressions were investigated by immunoperoxidase staining using mouse monoclonal IgG
antidody
against v-K-ras and v-H-ras encoded p21 protein product as primary antibody and abidin-biotin complex.
@ES The results were obtained as follows:
@EN 1. The incidne ces of DMH-induced colon cacer were 30% in groups I and II, 55% in group III. Overall 27 cases(23 animals) of colon cacers were observed, however only one colon cancer and 23% of polyps were detected in control group.
Histopathologically 51.9% of well differentiated, 37.0% of moderately differentiated and 11.1% of poorly differentiated or mucinous adenocarcinomas were observed.
2. The incidences of point mutation of 23 colon cancers were 34.8% of GAT, 17.4% of TGT, 17.4% of GTT mutation codon 12 and 30.4% of GAC mutation with overall 78.3% of mutations. But no mutation was observed in normal colon tissues.
3. The expression of p21 protein products of v-K-ras in DMH induced colon cancers was 74.1% of positive which is consisted with 11.1% of -type, 55.6% of C-type and 7.4% of S-type in 27 colon cancer tissues. C-type was gradually increased form
16.7% of
group I to 25.0% group II and 92.3% of group III, while A-type was changed from 16.7% of group I to 25.0% of group II and 0% of group III. Similarly the expression of v-H-ras was 74.1% of positive which is consisted of 11.1% of A-type, 59.3% of
C-type
and 3.7% of S-type in overall. C-type was increased from 16.7% of group I to 37.5% of group II and 92.3% of group III.
Positive expression was gradually increased from 33.4%(group I) to 62.5%(group II) and 100%(group III) in both v-K-ras and v-H-ras.
4. The positive p21 expressions were 71.4% in well differentiated and 90.0% in moderately differentiated carcinomas.
With above results, authors considered that point mutation of c-K-ras oncogene play a 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 predict of prognosis of colon cancers.
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