| Background:Cervical cancer is a common gynecological cancer. In recent years,women with cervical cancer annually added13million people, approximately28.8%of the total number of new cases around the world, and tended to be younger. If it isconfirmed by biopsy, majority of the tumor can be cut so completely that cansignificantly reduce mortality and recurrence rate of cervical cancer patients. Cervicalcancer is a a continuous process with slow progression, and patients has obviousrelevance with cervical human papillomavirus (human papillomavirus, HPV) infection,abortion frequency of sexual partners, age of first sexual intercourse multiple riskfactors, family history of cervical cancer, parity, geographic distribution, etc.Approximately99.7%of cervical HPV infection were seen, HPV infection hasbecome the main cause of cervical cancer. In this process, epithelial-mesenchymaltransition (EMT) often accompanied.EMT is that under the influence of certain factors, the connection of epithelial cellsdisintegrate, with the gradual loss of cell polarity and cytoskeletal remodeling, so thatthe polarity of epithelial cell loss, migration and athletic ability enhance, at the sametime the loss of epithelial phenotype gradually acquire mesenchymal phenotype.E-cadherin is a member of calcium-dependent adhesion molecules family in the celladhesion,and plays a key role in the normal maintenance of the epithelial phenotype.The reduction or loss of E-cadhein are the most important landmark changes in EMT.AKT is the most important downstream of PI3K signaling molecule, which is a serine/threonine kinase. Activated p-AKT induces the occurrence of epithelial tomesenchymal transition by AKT/GSK-3β/Snail pathway, promoting malignant invasion and metastasis.Incidence of cervical cancer is a gradual process, from cervical intraepithelialneoplasm(CIN) to cervical cancer,through CIN1,2,3progressive. During the process,occurrence of EMT cervical lesions and its possible signaling molecules is not veryclear. Therefore, we collected clinical cervical specimens of different stages,andanalyzed the relationship between the dynamic changes of expression of E-cadherinand levels of p-AKT phosphorylation in patients with clinical cervical lesions andcervical lesions. Further, combined with the detection of cervical intraepithelial relatedsignaling molecules and differentiation indexes,we investigate the possible molecularmechanisms, to provide laboratory evidence of improvement in the pathogenesis anddiagnosis and treatment of clinical cancer.Objective: To investigate the correlation between expression of E-cadherin and thelevel of phosphorylation of AKT and the degree of cervical lesions, and explore therelationship between EMT disease and progression and the possible signalingpathways.Methods: Collect20cases of normal cervical tissue,30cases of CIN tissues,50casesof cervical squamous cell carcinoma. Immunohistochemistry,Western blotting andQuantitative PCR were used to detect mRNA and protein expression of E-cadherin,β-catenin and Loricrin in tissue,and dectect the level of AKT phosphorylation indifferent cervical lesions at the same time. Then we analyzed correlation betweenE-cadherin expression and AKT phosphorylation levels,and the correlation betweentwo markers above and degree of cervical lesions and the differentiation of cervicalcancer. Results:(1) Immunohistochemistry showed that, with the progress of cervical lesions,expression of E-cadherin and Loricrin gradually decreased or absent (P <0.05); innormal cervical epithelium β-catenin expressed in the cell membrane, along with theprogress of cervical lesions, gradually from the membrane to the cytoplasm andnucleus transfer and expression rate decreased (P <0.05); expression of p-AKT isgradually increased with the disease progresses (P <0.05)(2) Western blotting results show that, with the progress of cervical lesions, expressionof E-cadherin, Loricrin and β-catenin gradually decreased, or absent (P <0.05);expression of p-AKT is gradually increased with disease progression (P <0.05), theresults consistent with immunohistochemistry.(3) Quantitative PCR results are also shown that with the progress of cervical lesions,mRNA expression of E-cadherin, Loricrin, β-catenin have a gradual decline all.(P<0.05),which is consistent with protein expression.(4) In cervical cacer, immunohistochemical and Western blotting results both showedthat with reduction of the degree of differentiation of tumor, E-cadherin, Loricrin,β-catenin expression gradually decreased, or absent (P <0.05); while phosphorylationlevel of AKT gradually rised higher with reduction of the degree of differentiation ofcervical cancer.(P <0.05)(6) Correlation analysis showed that expression of E-cadherin and stage of cervicallesions was negatively correlated (rs=-.688, P＜0.01) and p-AKT the expression of apositive correlation (rs=.462, P＜0.01).while squamous differentiation expression ofE-cadherin and stage of cervical lesions was positively correlated (rs=.438, P＜0.01)and p-AKT the expression of a negative correlation (rs=.462, P＜0.01; rs=.692, P＜0.01).(7) Expression of E-cadherin and AKT phosphorylation level was negatively correlated(rs=-.828, P＜0.01). Conclusion:(1) Loss of E-cadherin expression and increased of AKT phosphorylationclosely related with the development of cervical lesions;(2) Abnormal intracellular localization of β-catenin and abnormal activation of AKTplay a key role in EMT of cervical epithelial;(3) E-cadherin and p-AKT can be used to monitor the progress of cervical lesions andguide clinical treatment programs and prognosis. |
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