| Tumorigenesis involves a complicated multi-step processs. Investigation have revealed that uncontrolled cell cycle plays an important role in cell over-proliferation, which ultimately results in cell canceration. the strict phase change of cell-cycle regulatory is decided by serial cell cycle regulatory factors,the expression of these cell cycle regulatory factors depend on many kinds of related genes and co-restrict of cell cycle regulatory factors. dysfuctions exist in the two modules in tumorigenesis. To investigate the expression of these related genes and the relationgship between cell cycle regulatory factor is important to identify the tumorigenesis mechanism and oncotherapy. Cyclins,cyclin-dependent kinase(CDK) and cyclin-dependent kinase inhibitor(CKI)are endogenous components in cell-cycle regulatory. The transcription factors are activated by exterior and interior signals through kinds of transmission pathway,the activated transcription factors interact with cell cycle regulatory factors and related genes which participate in the regulation,and form a complicate regulation lattice. It can influence the quantity and protein kinase activity of cyclin,CDK and CKI, and fulfil the cell-cycle regulatory proceedings. Now more investigation on related genes were oncogene,as ras gene,myc gene et al. Macrophage migration inhibitory factor (MIF) was widely studied in recent years,now more and more investigations discovered that correlation may exists between tumorigenesis mechanism and MIF , which originally identified as a type of preinflammation cytokine. Overexpression of MIF protein was reported in human adenocarcinoma of lung,carcinoma of prostate and hepatocellular carcinoma tissue. The discovery of MIF in these cancers led to our hypothesis that it was intimate related to tumorigenesis, But the concrete mechanism remains to be confirmed. Now ongoing studies are in progress to investigate the mechanism by which MIF participate in tumorigenesis.Esophageal squamous cancer is one of the most fruquent malignant neoplasm in our country, to elucidate the mechanism of MIF in human esophageal squamous carcinoma will benefit to early diagnosis,therapy and the evaluation of prognosis. but the research on the mechanism of MIF in esophageal squamous cancer is still rare. So we not only study the relationship between abnormal expression of MIF and clinical significance of esophageal squamous carcinoma,but also the expression of p21,cyclinD1 protein in esophageal cancer and relationship between expression of p21,cyclinD1 and MIF protein. The abnormal expression of MIF may play an important role in carcinogenesis and progress of esophageal squamous carcinoma and provide some new ways in appraisal of prognosis and therapy for human esophageal squamous carcinoma.In this thesis, the following experiments are conducted:We use S-P immunohistochemical staining to determine the expression of MIF,p21,cyclinD1 in 80 cases of esophageal squamous carcinoma and 80 cases of peritumor esophagus tissue. And the expression of MIF mRNA in esophageal squamous carcinoma tissues and its corresponding peritumor esophagus tissue are detected by RT-PCR in 80 patients.1) The positive incidences of MIF expression in esophagus squamous carcinoma was97.5%, while in normal peritumor esophagus tissue it was 23.08%. It is remarkably significant in comparison between nomal peritumor esophagus tissue and esophageal carcinoma tissue. The expression of MIF was correlated with both tumor differentiation and the tumor TNM staging, but not correlated with patient age ,patient sex ,tumer size and lymph node metastasis.2) The positive incidences of p21,cyclinD1 expression in esophageal carcinoma were 81.25%,65%,while in normal peritumor esophagus tissue it were 22.5%,13.75%. they are remarkably significant in comparison between nomal esophageal tissues and esophageal carcinoma tissue.3) There was significant positive correlations between the expression of MIF and p21( P = 0. 01,r =+0.647),cyclinD1( P = 0. 01,r = +0. 544).4) The positive incidences of MIF mRNA expression in esophageal carcinoma was 85%, while in normal peritumor esophagus tissue it was 15%. It is remarkably significant in comparison between nomal peritumor esophagus tissue and esophageal carcinoma tissue.The expression of MIF was correlated with both tumor differentiation and the tumor TNM staging, but not correlated with patient age, patient sex, tumer size and lymph node metastasis.In conclusion, we proved that abnormal high level expression of MIF in esophageal squamous carcinoma tissue exists in transcription and translation.MIF may play an important role in esophageal squamous carcinoma pathogenesis. Significant positive correlations between MIF and p21,cyclinD1 shows that MIF accelerates the processs of cell cycle through increasing the expression of cyclinD1,and inhibiting p21 binds to cyclin-CDKs. The biological anti-oncogene activity of p21 was inhibited by MIF. These can offers a new thiking in gene therapy of human esophageal squamous cell carcinoma.
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