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J Korean Cancer Assoc > Volume 26(3); 1994 > Article
Journal of the Korean Cancer Association 1994;26(3): 399-409.
악성 및 악성 대장종양에서 p21 단백질의 발현
성기영, 김정수, 장석균, 전정수, 주상용
Expression of p21 Protein in Benign and Malignant Colorectal Tumors
Ki Young Sung, Jung Soo Kim, Suk Kyun Chang, g Soo Chun, Sang Yong Choo
ABSTRACT
Tumorigenesis from the benign and precancerous lesion has long been thought to be a multistep process. Among them, point mutation of ras oncogene was studied in several investigations as an initial event of tumorigeriesis of human colorectal cancer. Ras oncogene encoded protein product p21 has been known to regulate cell proliferation and differentiation by p21 GTP(guanosine 5-triphosphate) or GDP(guanosine diphosphate) complex with point mutation. Activation of cellular ras genes is caused by single base mutation resul- ting in sn amino acid substitution yielding p21 species with increased transforming ability. Immunohistochemical and molecular cytogenetic studies of colon and rectal neoplasms indicat- ed that in 40-50% of cases mutated ras oncogenes can be identified. But, the function of p21 has not been known precisely, yet. We undertook the immunohistochemical study of the ras p21 protein product in a series of normal colorectal tissues, benign tumors, colorectal cancers and metastatic lymph node tissues with K-ras and H-ras monoclonal antibody. Benign tumors were divided into three groups by dysplasia, size and pattern of nuclear arrangement and mucinous component in cytoplasm. Malignant tumors were dassified into 4 groups by Astler Collers modification of Dukes classifi- cation. The purpose of this study was to find out the importance and clinical application of malignant teansformation of benign tumors by detection of expression of p21 encoded by K-ras or H-ras oncogene. The results were obtained as follows: 1) The expression of the p2l of K-ras oncogene in normal tissues, benign tumors, malignant tumors and metastatic lymph nodes were 13.3%, 34.8%, 40.2% and 20.0%, respectively. And ex- pression of the p21 of H-ras were 13.3%, 50.7%, 16.7% and 35.0%, respectively. 2) The expression of the p2l of K-ras and H-ras in benign tumor was divided into 3 groups. And the rate of the group 1 showed lowest rate as 11.1% and 27.8%. The expression rate was in- creased to 40.0% and 80.0% in group 2, 61.5% and 69.2% in group 3. 3) The expression of the p21 in colorectal cancer was slightly different in various stages using the K-ras monoclonal antibody 50%, 50%, 33.3% snd 36%, repectively. But, the result of H- ras p21 was varied 58.3%, 70%, 70% and 64%, respectively. 4) In according to the differentiation of the colorectal cancer, the expression of the p2l K-ras was 44.4% in well differentiation group, 34.2% in moderate group, 46.1% in poorly group. In the case of p21 of H-ras, 75.0% in well differentiated group, 63.2% in moderate differentiated group and 53.9% in poorly differentiated group were evaluated. 5) In a point of intensity of staining, the proportion of strong stained specimen was slightly different in each group, but there was no significant discrimination statistically. With above results, authors considered that ras oncogene encoded protein product p21 plays an important role in colon and rectal carcinogenesis at the early stage, especially in the pro- gression of adenoma, and may be useful in early detection and prediction of progression of colorectal cancer.
Key words: p21 protein, K-ras, H-ras
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