Turkiye Klinikleri Journal of Medical Sciences

.: REVIEW
Mesane Kanseri Gelişiminde Moleküler Mekanizmaların Rolü
The Role of Molecular Mechanisms in the Development of Bladder Carcinoma: Review
Ertan ALTAYLIa, Sezgin GÜNEŞb
aTSK Sağlık Komutanlığı GATA, Ankara bTıbbi Biyoloji AD, Ondokuz Mayıs Üniversitesi Tıp Fakültesi, Samsun
Turkiye Klinikleri J Med Sci. 2011;31(1):191-205
doi: 10.5336/medsci.2009-13192
Article Language: TR
Full Text
ÖZET
Kanser türleri içinde önemli bir yer tutan mesane kanseri, Batı ülkelerinde yapılan çalışmalara göre sıklık sıralamasında erkeklerde dördüncü sırayla tüm kanserlerin %5-10'unu, kadınlardaysa sekizinci sıradaki yeriyle % 4'ünü oluşturmaktadır. Mesane kanserinin etiyolojisi, büyük oranda bilinmemekle birlikte, çevresel, demografik ve genetik faktörlerin etkili olduğu düşünülmektedir. Mesane kanserinin gelişiminde rol oynayan çevresel faktörler; sigara, mesleki karsinojenler, şistozomiyazis, kronik sistit, tedavi amaçlı siklofosfamid kullanımı ve pelvik radyoterapidir. Mesane kanserinin gelişiminde rol oynayan demografik faktörler cinsiyet, ırk ve yaştır. Mesane kanserinin gelişiminde çok sayıda onkogenlerin ve tümör süpresör genlerin çeşitli seviyelerdeki mutasyonları önemli rol oynamaktadır. Onkogenler, hücresel seviyede dominant etkiye sahip genlerdir; yani aktive edildiklerinde veya ekspresyon seviyeleri arttığında tek bir mutant allel, bir hücreyi normal fenotipten malign fenotipe dönüştürmeye yetebilir. Mesane kanseriyle ilişkili en iyi bilinen onkogenler; H-ras, erb-B2 ve c-myc'dir. Tümör baskılayıcı genlerse onkogenlerin tersine hücre çoğalmasını inhibe edici özelliktedir. Tümör baskılayıcı genlerin, kanser gelişiminde etkili olabilmesi için her iki allelinin fonksiyonunu yitirmesi gerekir ve dolayısıyla bu genler, kanser gelişimindeki etkileri bakımından resesif özelliktedirler. Kromozom 13q'daki retinoblastoma geni (Rb) ve kromozom 17p'deki p53 geni, en iyi çalışılmış tümör baskılayıcı gendir. Kanserin ilerlemesinde anjiyogenez gelişimi, hücre dışı matriks ve hücre adezyon moleküllerindeki çeşitli anormallikler etkili olmaktadır. Ayrıca mesane kanserinin gelişiminde ve ilerlemesinde, mikrosatellit kararsızlığıyla çeşitli epigenetik faktörlerin de etkili olduğu gösterilmiştir. Mesane kanserinin gelişiminde ve ilerlemesinde rol oynayan karmaşık mekanizmaların anlaşılması için yeni çalışmalara ihtiyaç vardır.

Anahtar Kelimeler: Mesane tümörleri; onkojenler; genler, tümör baskılayıcı; karsinojenler; mutasyon; hücre yapışma molekülleri; çok biçimlilik, genetik
ABSTRACT
Studies performed in Western countries has proven that the bladder carcinoma, which occupies an important place among all cancers, constitutes 5-10% of all male cancers and is the fourth most common cancer in males, while it is eighth most common cancer in females and constitutes 4% of all female cancers. Although etiology of bladder carcinoma is not clearly known, environmental, demographic and genetic factors are thought to be influential. The environmental factors that play role in the development of bladder carcinoma are smoking, occupational carcinogens, schistosomiasis, chronic cystitis, administration of cyclophosphamide for therapeutic purposes and pelvic radiotherapy. Demographic factors that play a role in the development of bladder carcinoma are gender, race and age. The mutations on the different levels of tumor suppressor genes and oncogenes have an important role in the development of bladder carcinomas. Oncogenes have dominant effects on cellular levels i.e when they are activated or their expression levels are increased, even a single mutant allel may be sufficient to convert a cell from normal phenotype to malignant phenotype. Well known oncogens that are related to bladder carcinoma are H-ras, erb-B2 and c-myc. On the contrary, tumor suppressor genes are inhibitors of cell proliferation. To be influential in the development of bladder carcinoma, both allelles of tumor supressor genes must lose their functions so that these genes are recessive in respect to their effects in the development of bladder carcinoma. The retinoblastoma gene (Rb) on chromosome 13q and p 53 gene on chromosome 17p are the most widely studied tumor suppressor genes. Abnormalities on angiogenesis, extracelllular matrix and adhesion molecules are effective in progression of cancer. In addition, microsatellite instability as well as various epigenetic factors are also shown to be effective in the progression and development of bladder carcinoma. Further studies are required for enlightening the complicated mechanisms of the development and the progression of bladder carcinoma.

Keywords: Urinary bladder neoplasms; oncogenes; genes, tumor suppressor; carcinogens; mutation; cell adhesion molecules; polymorphism, genetic

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30.03.2014

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