| Objective Lung cancer is the most common malignant tumor worldwide, with a high incident and mortality rate. However its carcinomatous mechanism is still unknown. Recently with the lucubrating the Oncology and Molecular Biology, people found that the DNA of the most malignant tumors would be aberrant including the activating of oncogenes and inactivating of tumor suppressor genes. Carcinomatous changing of normal cells result from the accumulation of genetic alterations at specific chromosomal regions involving a multistep process. Tumor suppressor genes are recessive genes. Their functions would not be found until the couple of the alleles lose or inactivate. While inactivating of tumor suppressor genes could make oncogenes express excessively, which would lead to cancer. So inactivating of tumor suppressor genes is a critical event to lung cancer pathogenesis. The main patterns include loss, mutation and methylation. Loss of heterozygosity (LOH) of 8p is an early and frequent event in lung cancers. Allelic losses on 8p have also been reported as an important genetic changing in many kinds of cancers, including prostate, breast, head-and-neck, esophageal and urinary bladder carcinomas. People always hope to find an important candidate tumor suppressor gene on 8p, just like finding FHIT on 3p, p16 on 9p and p53 on 17p. But until now people have not found a legal tumor suppressor gene on 8p which could exert effects in many kinds of tumors, this is not tally with the high frequent loss on 8p. When we studied 8p22 region and took LOH analysis, we noticed Fez1 (F37/Esophageal cancer-related gene-coding leucine-zipper motif) gene---a candidate tumor suppressor gene. We here take adenocarcinomas and accompanying nonmalignant tissues as the objectives for the study. Our goal is to investigate the two microsatellite sites inside or flanking to the Fez1 and its expression in pulmonary adenocarcinoma and their relationship to clinicopathological factors. Methods Our work is composed of three parts: (1) Microsatellite analysis was performed by using the primers (D8S261 and D8S233) that amplified polymorphic sequences inside or flanking to the Fez1 in the tumor tissues collected from 32 cases of primary adenocarcinoma. (2) Immunohistochemical S-P technique was performed to detect the expression of Fez1 protein in the tumor tissues and accompanying nonmalignant tissues. (3) Utilize Western blot to check the different expression of Fez1 in another 10 tumor tissues and accompanying nonmalignant tissues.Results For loci D8S261 and D8S233, LOH was found in informative cases was 60.0% (11/18) and 61.0% (9/15), respectively. Fez1 protein was 100% detectable in normal bronchial epithelium. The Fez1 protein was detectable in 33.33% of the samples, expression of Fez1 protein was down regulated in tumor tissue is 66.67%, the other 5 cases was not done. No correlation was found between the Fez1 protein expression and its clinicopathological parameters such as pathological group, clinical staging (p>0.05). The results of the Western blot show that the expression of the Fez1 in tumor tissues is obviously lower than normal tissues.Conclusion1. The result of Microsatellite analysis showed that a significant correlation between LOH of D8S261 and tumor grade(P<0.05).2. Scontaining protions of normal bronchial epithelium were uniformly positive in all cases. Overall in 27 informative cases, 66.67% (18 cases) primary tumors with reduced or absent Fez1 expression, compared with normal bronchial epithelium. In mixed tracheal glands, Fez1 express normally in serous alveoli and on expression in viscous alveoli. 3. The result of Western blot showed that the expressions of Fez1 in lung cancer and accompanying nonmalignant tissues were different.4. Loss of Fez1 expression is a frequent event in pulmonary adenocarcinoma and it may be one of the important candidate tumor suppressor gene in carcinogenesis of pulmonary adenocarcinoma. Its inactivation is attributable to several factors not only LOH of Fez1 gene but...
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