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Titolo:
LOCALIZATION AND EXPRESSION OF P27(KIP1) IN MULTISTAGE COLORECTAL CARCINOGENESIS
Autore:
CIAPARRONE M; YAMAMOTO H; YAO Y; SGAMBATO A; CATTORETTI G; TOMITA N; MONDEN T; ROTTERDAM H; WEINSTEIN IB;
Indirizzi:
COLUMBIA UNIV,COLL PHYS & SURG,HERBERT IRVING COMPREHENS CANC CTR,701W 168TH ST NEW YORK NY 10032 COLUMBIA UNIV,COLL PHYS & SURG,HERBERT IRVING COMPREHENS CANC CTR NEWYORK NY 10032 COLUMBIA UNIV,COLL PHYS & SURG,DEPT PATHOL NEW YORK NY 10032 UNIV SACRED HEART,CTR RIC ONCOL GIOVANNI XXXIII I-00168 ROME ITALY OSAKA UNIV,SCH MED,DEPT SURG 2 OSAKA 565 JAPAN
Titolo Testata:
Cancer research
fascicolo: 1, volume: 58, anno: 1998,
pagine: 114 - 122
SICI:
0008-5472(1998)58:1<114:LAEOPI>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEPENDENT KINASE INHIBITOR; CELL-CYCLE ARREST; TUMOR-SUPPRESSOR GENE; HUMAN ESOPHAGEAL CANCER; CDK INHIBITOR; POTENTIAL MEDIATOR; BREAST-CANCER; MICE LACKING; GROWTH; D1;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
71
Recensione:
Indirizzi per estratti:
Citazione:
M. Ciaparrone et al., "LOCALIZATION AND EXPRESSION OF P27(KIP1) IN MULTISTAGE COLORECTAL CARCINOGENESIS", Cancer research, 58(1), 1998, pp. 114-122

Abstract

The cyclin-dependent kinase inhibitor p27(Kip1) can inhibit the G(1) to S transition of the cell cycle and is a putative tumor suppressor. However, our laboratory found that a variety of human cancer cell lines express relatively high levels of this protein and that this is often associated with increased expression of cyclin D1 or cyclin E. Therefore, in the present study we analyzed by immunohistochemistry the expression of p27(Kip1) in a series of human tissue samples representing various stages of colon carcinogenesis, using 20 samples of normal colon mucosa, 20 hyperplastic polyps, 19 samples of adenomatous polyps, and 40 samples of various types of colorectal carcinomas. Parallel immunostaining was done for cyclin D1 and also for Ki67 to evaluate cell proliferation, An additional 17 human colon carcinoma samples, togetherwith paired adjacent normal mucosa samples, were analyzed for levels of expression of the p27(Kip1) protein by Western blot analysis, and 7of these pairs of samples were examined by Northern blot analysis forlevels of p27(Kip1) mRNA. We did not find a positive or negative correlation between p27(Kip1) expression and cell proliferation in the normal mucosa and tumor samples. There was, however, an inverse correlation between p27(Kip1) and Ki67 expression in the Lymphoid follicles present in the colonic mucosa. There was no evidence for a consistent increase or decrease in p27(Kip1) expression in the mucosal cells during colon carcinogenesis, because the mean values for percentage p27(Kip1)-positive cells were similar in the normal mucosa, adenomatous polyps,and carcinoma samples. This is in contrast to Ki67 and cyclin D1 expression, which did show significant increases in mean values with tumordevelopment. A subset (35%) of the carcinomas displayed diffuse cytoplasmic staining, in addition to nuclear staining, for p27(Kip1), and in these eases the percentage of cells that were positive for p27(Kip1)was higher than in cases that had only nuclear staining. There was a significant correlation between p27(Kip1) expression and tumor grade; i.e., well and moderately differentiated carcinomas had high p27(Kip1)expression, whereas poorly differentiated carcinomas had lower expression. The Western blot analysis data on p27(Kip1) expression confirmedthis correlation. Comparisons of Northern and Western blots did not show a correlation between the level of p27(Kip1) mRNA and the corresponding protein, a finding consistent with evidence that the p27(Kip1) protein is regulated mainly via a posttranscriptional mechanism. The immunostaining studies revealed a significant correlation between high p27(Kip1) protein expression and high cyclin D1 expression in the adenomatous polyps and in the subset of carcinomas that had only nuclear p27(Kip1) expression. This may reflect the existence of a homeostatic feedback mechanism that is lost in the high-grade carcinomas that express low levels of p27(Kip1).

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Documento generato il 28/11/20 alle ore 04:56:43