Title
Author
DOI
Article Type
Special Issue
Volume
Issue
Quantitative study on the correlation between p53 gene mutation and its expression in endometrial carcinoma cell lines
1Department of Clinical Cytology, Graduate School of Medical Sciences, Kanagawa
2Department of Pathology, Kanagawa
3Department of Obstetrics and Gynecology Tokyo Posts & Telecommunications Hospital, Tokyo, Japan
4Tissue Culture Center School of Medicine, Kanagawa
5Department of Clinical Cytology, School of Allied Health Sciences, Kitasato University, Kanagawa
*Corresponding Author(s): Y. Kamata E-mail:
Mutant p53 protein is not degradated but accumulates in the nuclei. However, the relation between p53 gene mutation and quantity of p53 protein has not been clarified yet in endometrial carcinoma. We investigated the correlation between p53 gene mutation and its protein expression quantitatively using 11 cell lines of endometrial adenocarcinoma, endometrioid type and two serous-type cell lines. To examine p53 mutation, PCR-SSCP analysis in exon 5 to 8 and direct sequence were carried out. p53 expression was determined by immunocytochemistry and immunoblotting. The percentage of positive staining in the nuclei by immunocytochemistry was calculated as a labeling index (LI). The amount of p53 detected by immunoblotting was expressed as a comparative value of Ishikawa cells. Point mutation of p53 gene was detected in four of 11 (36.4%) cell lines of endometrioid adenocarcinoma, and all two of serous adenocarcinoma. There was a significant positive correlation between p53 LI and p53 values. The LI and the values of p53 were significantly higher in the mutant group than the wild one, thus showing a quantitative correlation between p53 protein expression and p53 gene mutation in endometrial carcinoma cell lines. It is plausible that immunohistochemical analysis of p53 could be qualified to be a convenient indicator of p53 gene mutation on clinical materials, if p53 LI is more than 40 (M-SD in mutant p53).
p53; Endometrial carcinoma; Mutation; Immunoblotting; Immunocytochemistry; HEC-1-A; Ishikawa
Y. Kamata,J. Watanabe,H. Hata,M. Hamano,H. Kuramoto. Quantitative study on the correlation between p53 gene mutation and its expression in endometrial carcinoma cell lines. European Journal of Gynaecological Oncology. 2004. 25(1);55-60.
[1] Miller C., Mohandas T., Wolf D., Prokocimer M., Rotter V., Koeffler H. P.: "Human p53 gene localized to short arm of chromosome 17". Nature, 1986, 319, 783.
[2] Greenblatt M.S., Bennett W.P., Hollstein M., Harris C.C.: "Mutations in the p53 tumor suppressor gene: Clues to cancer etiology and molecular pathogenesis". Cancer Res., 1994, 54, 4855.
[3] Ashcroft M., Vousden K.H.: "Regulation of p53 stability". Oncogene, 1999, 18, 7637.
[4] Kubbutat M. H. G., Vousden K. H.: "Keeping an old friend under control: Regulation of p53 stability". Mot. Med. Today, 1998, 4, 250.
[5] Athanassiadou P., Petrakakou E., Liossi A., Nakopoulou L., Zerva C., Dimopoulos A., Athanassiades P.: "Prognostic Significance of p53, bcl-2, and EGFR in Carcinoma of the Endometrium". Acta cytol., 1999, 43, 1039.
[6] Reinartz J.J., George E., Lindgren B.R., Niehans G.A.: "Expression of p53, transforming growth factor alpha, epidermal growth factor receptor, and correlation with survival and known predictors of survival". Human Pathol., 1994, 25, 1075.
[7] Enomoto T., F ujita M., Inoue M., Rice J. M., Nakajima R., Tanizawa O., Nomura T.: "Alterations of the p53 tumor suppressor gene and its association with activation of the c-K-ras-2 protooncogene in premalignant and malignant lesions of the human uterin endometrium". Cancer Res., 1993, 53, 1883.
[8] Kohler M. F., Berchuck A., Davidoff A. M., Humphrey P. A., Dodge R. K., Iglehart J. D. et al.: "Overexpression and mutation of p53 in endometrial carcinoma". Cancer Res., 1992, 52, 1622.
[9] Salvesen H.B., Iversen O.E., Akslen L.A.: "Prognostic significance of angiogenesis and Ki-67, p53, and p21 expression: A population-based endometrial carcinoma study". J. Clin. Oncol., 1999, 17, 1382.
[10] Lax S.F., Kendall B., Tashiro H., Slebos R. J. C., Ellenson L. H.: "The frequency of p53, K-ras mutations, and microsatellite instability differs in uterine endometrioid and serous carcinoma evidence of distinct molecular genetic pathways". Cancer, 2000, 88, 814.
[11] Ito K., Sasano H., Matunaga G., Sato S., Yajima A., Nasim S., Garret C. T.: "Correlations between p21 expression and clinicopathological findings, p53 gene and patients with endometrial carcinoma". J. Pathol., 1997, 183, 318.
[12] Niwa K., Murase T., Morishita S., Hashimoto M., ltoh N., Tamaya T.: "p53 overexpression and mutation in endometrial carcinoma: inverted relation with estrogen and progesterone receptor status". Cancer Detec. Prev., 1999, 23, 147.
[13] Stewart R. L., Royds J. A., Burton J.L., Heatley M. K., Wells M.: "Direct sequencing of the p53 gene shows absence of mutations in endometrioid endometrial adenocarcinomas expressing p53 protein". Histopathology, 1998, 33, 440.
[14] Kuramoto H., Nishida M., Morisawa T., Hamano M., Hata H., Kato Y. et al.: "Establishment and characterization of human endometrial cancer cell lines". Annals N. Y. Acad. Sci., 1991, 622, 402.
[15] Uchida T., Wada C., Shitara T., Egawa S., Koshiba, K.: "Infrequent involvement of p53 gene mutations in the tumorigenesis of Japanese prostate cancer". Br. J. Cancer, 1993, 68, 751.
[16] Bodner S. M., Minna J. D., Jensen S. M, D'Amico D., Carbone D., Mitsudomi T. et al.: "Expression of mutant p53 protein in lung cancer correlates with the class of p53 gene mutation". Oncogene, 1992, 7, 746.
[17] Shahin M. S., Hughes J. H., Sood A. K., Buller R. E.: "The prognostic significance of p53 tumor suppressor gene alterations in ovarian carcinoma". Cancer, 2000, 89, 2006.
Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.
Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.
Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.
JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.
Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.
BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.
Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.
Top