Molekulare Aspekte des HarnblasenkarzinomsTeil 1

Zusammenfassung

Die Transformation einer normalen in eine maligne Zelle erfolgt über einen Mehr-Schritt-Mechanismus, der verschiedene molekulare und genetische Veränderungen beinhaltet. Diese molekularen Veränderungen entstehen spontan oder werden durch Karzinogene wie z. B. Naphtylamine (ein im Zugarettenrauch enthaltenes Karzinogen) ausgelöst. Diese Arbeit fasst einige der wichtigsten molekularen und genetischen Veränderungen beim Blasenkarzinom zusammen. Wie bei den meisten anderen malignen Erkrankungen wird auch Blasenkrebs durch eine Häufung verschiedener molekularer Veränderungen ausgelöst. Durch Mutation oder chromosomale Aberration kommt es zur veränderten Expression von Onkogenen (ras, erbB-2 und EGF-Rezeptor), Tumor-Suppressor-Genen (Rb, p53), Zell-Zyklus-Genen (p15, p16) und DNA-Reparatur-Genen. LOH der Chromosomen 9p und 9q hat sich als ein entscheidendes Ereignis bei der Transformation von normalem Urothel zu papillärem Übergangszellkarzinom erwiesen, während p53 primär bei der Entstehung des Carcinoma in situ von Bedeutung ist.

Abstract

The transformation of a normal into a malignant cell is a multi-step mechanism, which involves various alterations on the molecular and genetic level. These molecular alterations occur spontaneously or are induced by carcinogens (e. g. naphtylamine - a component of cigarette smoke and one of the most important carcinogens leading to bladder tumor carcinogenesis). This report summarizes some of the most important molecular and genetic alterations in bladder cancer. As in most other malignancies the generation of bladder cancer is caused by the accumulation of various molecular changes. The expression of oncogenes (ras, erbB-2 and EGF receptor), tumor-suppressor genes (Rb, p53), cell-cycle genes (p15, p16) and DNA-repair genes is altered mostly by mutation or chromosomal abberation. Loss of heterozygosity of chromosome 9p and 9q has been shown to be a crucial event in the transition of normal urothelium to papillary transitional cell carcinoma, while p53 is primarily involved in the development of carcinoma in situ.

Key words:

Urogenital neoplasms - Bladder neoplasms - Genetics

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