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Study Of PTEN Protein And Related Factors In Colorectal Cancer And Gastric Cancer

Posted on:2004-08-08Degree:DoctorType:Dissertation
Country:ChinaCandidate:X L LiFull Text:PDF
GTID:1104360092995815Subject:Oncology
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PrefaceColorectal cancer and gastric cancer are two malignant tumors which have higher incidence in gastrointestinal tract and the incidence and mortality are increasing. The unlimited growth and metastasis of tumor cells is the most important feature. It is the major reason for gastric cancer and colorectal cancer patients'failure to be cured and dead. The growth and metastasis of tumors are regulated by many oncogenes and suppressor genes.PTEN gene is tumor suppressor gene which has been recognized in recent years. PTEN gene encodes a dual specificity phosphatase with lipid and protein phosphatase. Its lipid phosphatase dephosphorylates phosphtidylinositol (3,4, 5) - triphosphate ( PIPS ) , which is intracellular second messenger of growth factors such as insulin growth factor and epidermal growth factor. The function of PTEN decrease the concentration of PIPS and suppressed the activity of Akt. Finally, it inhibits the growth and apoptosis of cells. PTEN function as protein phophatase has been implicated in the inhibition of cell migration and invasion via dephosphorylation of focal adhesion kinase, a molecule critical in the regulation of integrin signaling and also in the inhibition of cell cycle progression. It has been shown that PTEN protein can be reduced or absent in different degrees.EGFR/erbB -1 ,HER2/erbB -2 belong to members of subtype I receptor tyrosine kinases which are transmembrane glycoproteins with intrisic tyrosine ki-nases. These tyrosine kinases determine multiple biological function such as cell growth, differentiation, migration and survival. The major signaling route of the EGFR family is the ras - raf - MAP - kinase pathway. Another important pathway is that constituted by PI - 3 - kinase and the downstream protein kinaseAkt. When receptors combine with cogent ligand, they will form homodimerza-tion and/or heterodimerization. Dimerization causes a conformational change that activates the kinase domain, leads to autophosphorylation and initiation of divergent signal transduction cascades. Then the signals are transducted to transcription factors and influence the function of different genes. As EGFR and c -erbB -2 are crucial in signaling, the importance and practility that target to the abnormal signal tranduction have been realized. To date, the erbB - targeted therapy has been put into practice in clinical. Therefore assessing the status of protein expression and gene amplification is an important thing for selecting cases to be carried out individual therapy.E - cadherin is a group of transmembrane glycoproteins which mediated ho-mophilic cell - cell adhesion molecules and expressed in epithelial cells. E -cadherin is a kind of key molecules that establish and maintain intercellular connections and control cell polarity. Cancer cells with higher expression of E -cadherin, which are tightly connected each other, are not easy to get rid of from primary tumors. When E - cadherin is reduced expression or deletion, there is no adhesion among homophilic cells. These will facilitate cancer cells to invasion and metastasis. It has been shown that the abnormal expression of E - cadherin is correlated with the progression of gastric cancer.AimsTo observe the protein expression of EGFR and C - erbB - 2 as well as the status of their gene amplification in colorectal cancer, compare the relationship between the protein expression of EGFR, c - erbB - 2 and PTEN, and the significance of gene amplification in predicting target therapy in colorectal cancer. In addition by studying protein expression of ECD, an important adherin molecules , and PTEN in gastric cancer we tried to investigate their functions in invasion and the relationship between biological behaviors and prognosis, expected to find molecular biological markers in predicting the metastastic potential of gastric cancer and provide a scientific data for clinical treatment.Methods122 paraffin - embedded colorectal cancer specimens of resected specimen were collected. Detecting expressions of PTEN, C - erbB - 2...
Keywords/Search Tags:PTEN, EGFR, c-erbB-2, ECD, Protein expression, Gene amplification, Gastric cancer, Colorectal cancer, IHC, FISH
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