Dissertation > Excellent graduate degree dissertation topics show

Correlations among Expression Levels of FBX4, CCND1 and hTERT in Non-small Cell Lung Cancer Tissue

Author: WangZhiTian
Tutor: HuJian
School: Zhejiang University
Course: Surgery
Keywords: Fbx4 protein Cyclin 1 Human telomerase reverse transcriptase Lung cancer
CLC: R734.2
Type: Master's thesis
Year: 2010
Downloads: 90
Quote: 1
Read: Download Dissertation

Abstract

Background: Lung cancer has become the morbidity and mortality of the fastest growing, serious harm to human health and life of malignant tumors. Recent studies found that: the ubiquitin - proteasome pathway (ubiquitin-proteasome pathway) in malignant tumors, abnormal The unlimited proliferative cells and immortalized one of the reasons. The ubiquitin-proteasome pathway is a newly concern the regulation of protein degradation and function of critical systems. Its main role in the intracellular half-life of short adjust the abnormal protein and structural the hamartoma or damage protein. The process is covalently links multiple ubiquitin molecules (ubiquitin), the formation of multi-ubiquitin chain target protein ubiquitination, ubiquitination, transported to the 26S proteasome digestion and degradation. The ubiquitin is a polypeptide consisting of 76 amino acids, it through three ubiquitination enzyme interaction with the the target target protein binding, thereby causing the degradation of the target protein. Three ubiquitin enzyme ubiquitin activating enzyme (theubiquitin-activating Enzyme E1), ubiquitin-conjugating enzyme (ubiquitin-conjugating enzyme, E2) and ubiquitin ligase (ubiquitin ligase E3). E1 uses ATP to activate ubiquitin and transfer the activated ubiquitin to E2, where E2 with E3 ubiquitin molecules, so that in combination with the substrate. SCF ^{Fbx4/αB-crystallin enzyme is an important one in the E3 enzymes, which consists of Skp1, Cull, F-box protein 4 (Fbx4) and the αβ lens protein (αβ-crystallin), of which Fbx4 The protein the SCF ^{Fbx4/αB-crystallin important part of the enzyme, it can adjust the dimerization SCF ^{Fbx4/αB-crystallin enzyme activity, as and FBX4 protein a substrate specificity of the receptors, whereas the remaining components of this enzyme is common to the type of substrate reaction. Recent study found that over-expression of FBX4 caused the CCND1 ubiquitination CCND1 so as to promote the metabolism. If the SCF ^{Fbx4/αB-crystallin enzyme dysfunction and weakening the CCND1 ubiquitination, and promote CCND1 overexpression and accelerated cell cycle progression, which may lead to tumor formation. This perspective, a recent study found a FBX4 expression in a series of CCND1 overexpression of early human tumor cell lines is reduced, these tumors include: prostate cancer, thyroid cancer, and breast cancer. Cyclin D1 (Cyclin D1, CCND1) is the most important members of the G1 cyclin family, for the currently accepted oncogene in human esophageal cancer, head and neck cancer, breast cancer, have been found to be overexpressed and some cancers CCND1 expression is considered to be an early event, causing the formation of cancer. Human telomerase reverse transcriptase (human telomerase reverse transcriptase, hTERT), telomerase one of the core components, it can not be ignored key role in the tumorigenesis and development process. CCND1 and expression of hTERT and patients with important clinical pathology parameters in non-small cell lung cancer have been reported on amount of fbx4 expression in non-small cell lung cancer patients clinicopathological parameters the correlation between the relationship with the the CCND1 expression amount and hTERT expression between the amount of the studies have not been reported. This problem has attracted wide interest, but also the study was designed. Objective: To reveal the mechanism of action and lung cancer Fbx4 gene in lung cancer may occur progress mechanism to provide experimental basis. : Real-time quantitative PCR (real-time PCR) detection of 40 cases of lung cancer and its the adjacent tissues Fbx4 and CCND1 mRNA levels, Qualitative PCR Detection of hTERT mRNA levels. Statistical analysis SPSS16.0 software complete measurement data data represents the mean ± standard deviation (Mean ± SD) of all measurement data are first single sample KS normality test, t-test is a normal distribution, such as a non-normal distribution, non-parametric tests (rank-sum test). Count data using the chi-square test, ask each group of indicators using the chi-square test. P <0.05 was considered statistically significant. Results: Qualitative PCR results showed that: hTERT expression in lung cancer, no expression in normal tissues. Compared with adjacent normal tissue, lung tissue was significantly higher expression (P <0.01). Real-time PCR results: Fbx4 the expression in lung cancer and adjacent normal tissue within the organization, but compared to adjacent normal tissue the lung tissue Fbx4 expression slightly reduced, there is no statistically significant difference (P> 0.05). CCND1 only in the 12 patients with lung cancer and adjacent tissue detected in the remaining 28 cases of lung cancer and adjacent normal tissues showed no CCND1 expression, compared to normal tissues, lung cancer CCND1 decreased expression, there is no statistically significant difference (P > 0.05). The expression of fbx4 with the patient's age, gender, lung cancer TNM staging, tissue types of lung cancer, CCND1 expression levels and hTERT expression were no significant correlation. Conclusion: In this experiment, lung carcinoma and adjacent tissues, research FBX4 the CCND1 and hTERT expression correlation. The results showed that hTERT and the occurrence of cancer closely related to, CCND1 and hTERT may not be mediated ubiquitination by the Fbx4 degradation in lung cancer, this finding may be to clear further study of lung cancer direction provides some theoretical basis and experimental support.}}}}

Correlations among Expression Levels of FBX4, CCND1 and hTERT in Non-small Cell Lung Cancer Tissue

Abstract

Related Dissertations