Maspin, neuer Protease-Inhibitor mit Tumorsuppressor-Aktivität beim Brustkrebs

Zusammenfassung

Maspin (mammary serpin) ist ein neuer Serin-Protease-Inhibitor mit Tumorsuppressor-Aktivität beim Brustkrebs. Das entsprechende Maspin-Gen wurde ursprünglich durch subtraktive Hybridisierung identifiziert und konnte auf dem Chromosom 18 lokalisiert werden. Maspin zeigt starke Expression in normalen Brustepithelzellen bei überwiegender Down-Regulation in Brustkrebszellen. Maspins Expression sinkt kontinuierlich mit steigendem Malignitätsgrad von normalem Brustepithel über duktales Carcinoma in situ und invasive Karzinome bis hin zu Lymphknotenmetastasen und peripheren Metastasen. In-vitro-und In-vivo-Untersuchungen ergaben eine hemmende Wirkung von Maspin auf Tumorzellinvasion und Metastasierung. Die unterschiedliche Expression von Maspin in normalem Brustepithel und Brusttumoren beruht auf regulatorischen Veränderungen auf Transkriptionsebene. Damit unterscheidet sich Maspin von den klassischen Tumorsuppressor-Genen (z. B. P53, Retinoblastom) und kann der sogenannten Klasse II Tumorsuppressor-Genen zugerechnet werden. Die Tumorsuppressor-Gene der Klasse II besitzen eine besondere klinische Relevanz, da eine therapeutische Intervention im Sinne einer Re-Expression des Maspin-Gens durch medikamentöse (Gen-)Therapien möglich ist.

Summary

Maspin (mammary serpin) is a novel serine protease inhibitor related to the serpin family with tumor suppressing function in breast cancer. Maspin was originally identified from normal mammary epithelium by substractive hybridisation and might function as a class II tumor suppressor gene. Maspins decreased expression with increased level of malignancy and its loss in metastatic cells is regulated at the transcriptional level. Transfection of tumor cells with maspin cDNA inhibits invasion and motility and decreases tumor growth and metastatic ability in nude mice. The progressive loss of expression of maspin during tumor progression makes this novel protein an interesting diagnostic and prognostic marker. The reexpression of maspin by pharmacological intervention potentially offers a promising approach as a therapeutic option in breast cancer therapy.

Schlüsselwörter

Protease-Inhibitor - Maspin - Tumorsuppressorgen - Brustkrebs

Key words

Protease inhibitor - Maspin - Tumor suppressor - Breast cancer

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