Cancer Research and Treatment

Original Articles

Expression of p21/WAF1/CIP1, p27/KIP1 and p57/KIP2 Proteins in Gastric Adendegrees Carcinoma: Young Euy Park, Young Hee Choi, Kyoung Chan Choi, Seoung Wan Chae, Hyung Sik Shin; J Korean Cancer Assoc. 2000;32(3):457-466.

Abstract PDF: PURPOSE
p21/WAF1/CIP1, p27/KIP1 and p57/KIP2 are negative regulators of the cell division cycle. We evaluated the expressions of KIP CDK inhibitors and examined the relationship of clinicopathologic parameters and cell proliferation index in gastric adendegrees Carcinomas.
MATERIALS AND METHODS
The study was carried by the TUNEL method for apoptosis, immuno histdegrees Chemical staining for PCNA, p53, p21/WAF1/CIP1, p27/KIP1, and p57/KIP2 proteins and Western blot for KIPs proteins of normal and cancer tissues of stomach.
RESULTS
In normal gastric mucosa, p21/WAF1/CIP1 and p27/KIP1 proteins were expressed both mainly to the superficial portion of the glands with intestinal metaplasia and stromal cells. p57/KIP2 protein was also expressed normal crypt glandular epithelial and stromal cells. In gastric adendegrees Carcinoma, p21/WAF1/CIP1 was positive in 25 of 70 (35%) and showed significant decrease in deep tumor invasion (p=0.015) and the presence of angioinvasion (p=0.013). There was signi ficant inverse correlation between p27/KIP1 expression and cell proliferating index. p21/WAF1/ CIP1 expression was related to lower apoptotic index. Western blot analysis of KIP CDK inhibitors showed marked down-regulation of p21/WAF1/CIP1 protein in cancer than normal tissue, but alternative expression in p27/KIP1 and p57/KIP2 proteins.
CONCLUSION
The above results indicated that the expression loss of KIP CDK inhibitors was contributed to tumor progression and aggressiveness in gastric adendegrees Carcinoma.

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Expression of p53, p21/WAF1, bcl-2 and Loss of Heterozygosity for the Study of Apoptosis in Gastric Carcinoma: Hang Jong Yu, Joo Ho Lee, Woo Ho Kim, Kuk Jin Choe, Jin Pok Kim; J Korean Cancer Assoc. 2000;32(3):447-457.

Abstract PDF: PURPOSE
The purpose of this study was to correlate the immunohistdegrees Chemical expressions of p53, p21 and bcl-2, with their loss of heterozygosity (LOH) and clinical significance.
MATERIALS AND METHODS
Paraffin-embedded tissue sections from 30 patients with gastric car cinomas were examined for immunohistdegrees Chemical staining and LOH study. Primary antibodies used in immunohistdegrees Chemical staining were mouse mondegrees Clonal antibody to human p53, p21/ WAF1 and bcl-2. For PCR-LOH assays, D6S271, D6S105, D18S386, TP53, D17S796, and D17S786 microsatellite markers were used.
RESULTS
The expression rates of p53, p21 and bcl-2 were 76.7%, 80% and 3.3%, respectively. The expression of p21 was correlated with lymph node metastasis. LOH were found in 20.8% at D6S271, 42.3% at D6S105, 31.6% at D18S386, 39.1% at TP53, 40.9% at D17S796, and 50.0% at D17S786. No correlation was found between the immunohistdegrees Chemical expression and the LOH in these gene sites.
CONCLUSION
p53 and p21 were detected in high rate, whereas bcl-2 expression rate was very low in gastric adendegrees Carcinoma. Of them, overexpression of p21 was correlated with the tumor progression. High incidence rate of LOH may play an important role in gastric carcinogenesis. These findings suggest that the effects on apoptosis and cell cycle by p53 and p21 were important in development and progression of gastric cancer.

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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; J Korean Cancer Assoc. 1994;26(3):399-409.

Abstract PDF: 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.

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