The natural tumor suppressor protein maspin and potential application in non small cell lung cancer.
ABSTRACT The grim prognosis of lung cancer, that has an overall 10-15% survival at 5 years, remains in the US the leading cause of cancer mortality, provides a compelling rationale for studying the molecular basis of this malignancy. Surmising the common, general association with smoking, lung cancers differ at the microscopic, anatomical, epidemiological and clinical level and harbor complex genetic and epigenetic alterations. Currently, lung cancer is divided into small cell lung carcinoma (SCLC) and non small cell lung carcinoma (NSCLC) for the purpose of clinical management. (NSCLC) constitutes 80-85% of lung cancers and is further divided into histological subtypes such as adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, etc. The ultimate goal for lung cancer research is to develop a strategy to block the tumor progression and improve the prognosis of lung cancer. This goal can realistically be achieved only when the biological complexity of this disease is taken into account. To this end, identification and understanding of molecular markers that are mechanistically involved in tumor progression is needed. Our recent studies suggest histological subtype-dependent distinct correlations between the expression and/or subcellular localization of tumor suppressive maspin with the progression and prognosis of NSCLC. Maspin is an epithelial specific member of the serine protease inhibitor (serpin) superfamily but recently identified as an endogenous inhibitor of histone deacetylase 1 (HDAC1). This novel biochemical activity coincides with a consensus emerged recently from the evidence that nuclear maspin confers better differentiated epithelial phenotypes, decreased tumor angiogenesis, increased tumor sensitivity to drug-induced apoptosis, and a more favorable prognosis. In the current review, we discuss the evidence that maspin may be a marker that stratifies the progression and prognosis of different subtypes of NSCLC.
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ABSTRACT: Non small cell lung cancer (NSCLC) is a highly aggressive malignancy with survival rates limited to some patients in early stages (I and II). Apoptosis resistance is a hallmark of solid tumors that is tightly concerned with their biology. We analyzed the expression of 84 apoptosis-related genes in a group of Bulgarian patients with early-stage NSCLC. RNA samples extracted from 12 early-stage NSCLC patients [five squamous cell carcinomas (SCC) and seven adenocarcinomas (AC)] and eight adjacent non neoplastic pulmonary tissues were used for gene expression analysis. We applied pathway-focused expression profiling of 84 apoptosis-related genes using real-time PCR. Apoptosis-related genes down regulated in NSCLC compared to non tumor lung tissue (p <0.05) included representatives of the tumor necrosis factor (TNF) ligand family [TNF superfamily 8 (TNFSF8)], caspase cascade (CASP8 and CASP10) and caspase recruitment domain (CARD) family (BCL10), the positive apoptosis regulator DAPK1 and BCL2 family member MCL1. The potential of apoptosis-related genes as prognostic and predictive markers should be validated in future studies.