ISSN: 1300-0292
İndekslendiği Dizinler: SCIENCE CITATION INDEX EXPANDED
CINAHL, Index Copernicus,
Chemical Abstracts (CA),
Excerpta Medica / EMBASE
Dil: Türkçe, İngilizce
İçerik: Orijinal Araştırma, Derleme, Editöre Mektup, Olgu Sunumu, Tıp Eğitimi, Tıbbi Kitap İncelemeleri
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P53 As A Key In The Understanding Of Urothelial Carcinogenesis
Enver ÖZDEMİR*
*Yrd. Doç. Dr. Dicle Üniversitesi Tıp Fakültesi Üroloji AD, DİYARBAKIR
The cumulated results of researches on cancer have led to new dimentions in the early diagnosis, effective treatment and determination of prognosis of the disease. Oncogene activation and functional tumor suppressor gene loss are important steps in malignant transformation. Inactivation of p53 tumor suppressor gene is responsible from more than 50% of human neoplasms. P53 gene encodes a nuclear phosphoprotein which binds to the promotor regions of the other genes and transactivates them. DNA damage leads to the overexpression of p53 which arrests cell cycle at G1-S check point, and gives a chance to them for a selection between DNA repairment and apoptosis. Genomic instability caused by functional p53 loss results in neoplastic transformation or cell death.
In this article, we have summarized our studies on p53 in urothelial carcinomas in the light of the literature. Inactivation of P53 and continious overexpression of MDM2 which also seemingly results in the inactivation of p53 without gene alteration were responsible from 65% of the urothelial carcinomas. Our results suggested that the genomic instability produced by functional p53 loss up-regulated metalloproteinases and resulted in degradation of basement membranes underlying urothelial carcinomas, which forms first structural barrier to tumor invasion and metastsis. Moreover, we suggested that immunocytochemical analyses of p53 and mdm2 of primary cultures of exfoliated cells in the urine from patients with urothelial carcinomas is useful for intensive follow-up and effective treatment of the disease.
Keywords: P53, MDM2, Type IV collagen, Metalloproteinases, Urothelial Carcinomas
Turkiye Klinikleri J Med Sci 1998, 18:277-284
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