| Summary: | 碩士 === 國立中興大學 === 生物醫學研究所 === 93 === Recently, lung cancer has dominantly increased and ranked up to the first place among Taiwanese women died from cancers. Metastasis is a very complex process that involves cell adhesion, migration, invasion and degradation of the surrounding extracellular matrix. Many studies on cancer metastasis have been conducted, and several molecules participating in tumor cell invasion and metastasis have been identified, such as CD44, MMPs, TIMPs, and E-cadherin. However, molecular aspects of metastasis are not clearly understood. To obtain metastatic ability, tumor cells require the coordinated expression of metastasis-promoting genes and down-requlation of metastasis suppressing genes. It is necessary to identify the possible genes associated with cancer invasion and metastasis. Microarray is a powerful tool for screening a large number of genes expressions. By using an invasion/metastasis cell line model and microarray in a previous study, we have identified a tumor suppressor candidate, Human Liver DnaJ-like heat shock protein (HLJ1), which can suppress cancer cell invasion and growth. It is a member of the 40-kDa-heat shock protein family.
To identify the role of HLJ1 in lung adenocarcinoma cells, CL1-0 cells were transfected by RNA interference and silenced cell lines were selected in this study. The establishment of HLJ1-silenced cell lines may assist to further investigate functional characterization and molecular mechanism of HLJ1 subsequently. In addition, we want to find out proteins which were influenced by HLJ1. We have selected four cell lines that HLJ1 expression was stably suppressed. We used MTT, invasion, migration and colony formation in soft agarose analysis to determine the cellular functional characterization. The results showed that the reduced expression of HLJ1 could promote cell invasion, migration and anchorage independent growth. To investigate the mechanism of HLJ1 during the process of lung cancer cell migration and invasion, we performed the real-time RT-PCR and Western blotting analyses. The HLJ1-silenced CL1-0 cells could increase the phosphorylation of ERK as compared with scramble and parental CL1-0 controls, while E-cadherine expression is decreased. These findings suggest that HLJ1 can suppress cancer cell invasion ability via regulation of E-cadherine expression.
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