Exploring the Expression of 9 Circadian Genes in Adenocarcinoma of Lung

• Main Authors: Chu-Hsien Wang, 王竹賢
• Other Authors: Jan-Gowth Chang
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/08671214880038051248

碩士 === 中國醫藥大學 === 醫學研究所 === 93 === 英文摘要 Lung cancer is one of the most lethal cancers known to human because of the high incidence of the disease and the high fatality rate. In Taiwan, lung cancer is the leading cause of death in women and the second cause of cancer death in men. Adenocarcinoma , accounting for 35% of lung cancers in men and 69% of lung cancers in women in Taiwan, is the most prevalent type of lung cancer . Recent studies have shown that the molecular mechanism of carcinogenesis of the lung cancer involves several pathways. The mutated circadian clock genes have been implicated with carcinogenesis. There are at least eight circadian genes which have been identified: PERIOD 1 (Per1), PERIOD 2 (Per2), PERIOD 3 (Per3), CRYPTOCHROME 1 (Cry 1), CRYPTOCHROME 2 (Cry 2), CLOCK, BMAL1, AND CASEIN KINASE I (CkI). Studies of animal models and human tumor samples have revealed that the disruption of circadian rhythms is an important endogenous factor that contributes to mammalian cancer development. In this study, we try to explore the roles of Per1, Per2, Per3, Cry1, Cry2, Clock, Bmal1, Ck1ε and Tim in the development of adenocarcinoma of lung .by means of real-time quantitative RT-PCR and methylation-specific PCR to compare the difference of circadian genes expression between lung adenocarcinoma tissue and lung non-tumor tissue. 30 resected primary adenocarcinoma of lung and paired non-cancerous tissue samples are obtained from patients of the Changhua Christian Hospital. Our results showed that the mRNA levels of 7 of the 9 circadian genes, except Per3 and Tim, in cancerous tissues were statistically significantly decreased compared with those in paired non-cancerous tissues. The immunohistochemical staining showed the circadian proteins expression were mostly heterogeneous and varied in different cancer cell populations within the same specimen and the circadian proteins expression were mostly homogeneous in the non-cancerous cell population . Several asynchronized circadian clockworks may be in operation in the same cancer tissues. From promoter methylation study, promoter methylation was detected mainly on Cry1 gene. The promoter methylation and unmethylation status of Cry1 gene cannot account for the Cry1 mRNA level . In conclusion, the circadian rhythm is dysregulated in cancer tissue and well regulated in non-cancerous tissue. However, the methylation of the circadian genes does not have a significant role in the dysregulation of circadian genes of lung adenocarcinoma.