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The Expression Of PEPK And C-fos Protein In Cervical Carcinoma And Their Correlation

Posted on:2012-03-30Degree:MasterType:Thesis
Country:ChinaCandidate:J LinFull Text:PDF
GTID:2154330335478556Subject:Obstetrics and gynecology
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Cervical carcinoma is a very common gynecologic malignant tumor just inferior to breast carcinoma in women globally. Morbidity stands first on the list in some developing countries. In recent years, occurrence of cervical carcinoma shows younger trend. It threatens the fertility of women, even their lives. So it is very important to research the molecular mechanism which leads to the occurrence of cervical cancer to provide theoretical basis for the early diagnosis of cervical carcinoma and effective treatments.It is reported that the occurrence of tumor is closely correlated with information transfer in cells. MAPK(mitogen-activated protein kinase,MAPK) signal pathway is the important signal transmission system in cells, which is many signal transmission pathways'focal point and co-channel. There are three different types of MAPK:the extracellular-signalregulated kinases (ERK), c-Jun N-terminal kinase (JNK), P38 mitogen -activated protein kinase (P38 pathway). The ERK pathway is one of the most important and classical pathways of MAPK.Several lines of evidence indicate that overexpression and activation of ERK play an important role in growth, proliferation, differentiation, progression of cells. PERK is the phosphorylation of ERK, which is the activated form of ERK and the activation marker of the ERK pathway.c-fos's fixed position is at the chromosome 14q21- 31, c-fos is a cancer gene which codes to check nuclear protein, belongs to the early gene.The protein outcome has 380 amino acids.c-fos protein has no function alone.c-fos protein must become a different source dimmer with c-jun protein,then it has transcribe activation, therefore is as well as called transcribe factor (AP-1).The AP-1 can integrate many genes'promoter and enhancer which are related with tumors'occurrence and development,it can case target genes'expression then induce the occurrence of tumor. It can promote cell growth and divide,even induce tumor conversion.Objective: recent studies showed that in the stomach cancer, laryngo carcinoma, ovarian cancer,skin squamous cell carcinoma,the expression and activity of PERK, ERK, c-fos were nomal. However, reports about ERK signal pathway in human cervical cancer cells are few. No report about the PERK expression in cervical carcinoma tissue was found in our nation so far. This research focuses on PERK as a marker of ERK pathway activation, immuno- histochemistry was adopted to detect the expression of PERK,c-fos protein in the human cervical carcinoma tissues ,to discuss the expression of c-fos protein in the human cervical carcinoma and its relationship with the ERK signal pathway, to further provide the theoretical basis for therapy of cervical carcinoma.Method:100 cases of paraffin-embeded cervical tissues were selected between 2007~2010 from the Hospital of HeBei University , the NO.1 Middle Hospital of BaoDing and the Third Hospital of HeBei Medical University , with a completed approvement of pathological diagnosis following the surgery. These include 40 cases of cervical carcinoma group (A group), 30 cases of CIN group (B group), 30 cases of normal cervix group (B group). The A group including 20 well differentiated cases(A1 group)and 20 poorly differentiated cases (A2 group).And there are 18 cases with lymphonodus metastasis (A3 group), 22 cases without lymphonodus metastasis (A4 group). All the patients did not receive chemotherapy before surgery. The expression of PERK and c-fos were detected by immunohistochemistry in all specimens.The experimental results were analyzed by comparing the rate of multiple samples to chi-square test and correction chi-square test with SPSS 13.0. It was statistically significant (P <0.05) between three groups; compare with each other, P<0.0125 statistically significant. Correlation analysis using Spearman's rank correlation level of information , r = 0 for judging the relevance of existing standards. Results:1 The expression and localization of PERK protein in cervical tissues: PERK protein was located in the nucleus and cytoplasm, almost located in the nucleus .The expression rates of PERK in A group,B group and C group were 70%, 36.7%, 3.3% respectively. There were significant differences among the three groups (P<0.05). The expression rate of PERK in A group was significantly higher than those in B group and C group (P<0.0125), while the expression of PERK in B group was significantly higher than C group (P<0.0125). The expression rate of PERK in A1 group was 85%, which was significantly higher than those in A2 group's 55% (P <0.05). The expression rate of PERK in A3 group was 88.9%, which was significantly higher than those in A4 group's 54.5% (P <0.05).2 The expression and localization of c-fos protein in cervical tissues: c-fos protein was located in the nucleus .The expression rates of c-fos in A group,B group and C group were 57.5%, 23.3%, 0% respectively. There were significant differences among the three groups (P <0.05). The expression rate of c-fos in A group was significantly higher than those in B group and C group (P <0.0125), while there was no significant difference was found between the B group and C group (P=0.016). The expression rate of c-fos in A1 group was 95%, which was significantly higher than those in A2 group's 45% (P <0.05). The expression rate of c-fos in A3 group's was 77.8%, which was significantly higher than those in A4 group's 40.9% (P <0.05).3 The correlation of the expression of PERK protein and c-fos protein in cervical carcinoma: the expression of PERK protein was positive correlated with c-fos protein in cervical carcinoma tissues (rs= 0.430 P<0.05).Conclusions:1 The expression rates of PERK and c-fos in cervical carcinoma tissues were significantly higher than those in CIN tissues and normal cervix tissues. It predieted that the over expression of PERK and c-fos protein might be related to the occurrence of invasive cervical carcinoma,which might provide the basis for early diagnosis of invasive cervical carcinoma.2 The expression rates of PERK and c-fos in well differentiated cervical carcinoma tissues were higher than those in poorly differentiated tissues, cervical carcinoma tissues with lymphonodus metastasis were higher than cervical carcinoma tissues without lymphonodus metastasis. The high expression of PERK and c-fos protein may be play a promoting role in cervical carcinoma differentiation and metastasis.3 The PERK protein was positive correlated with c-fos protein in cervical carcinoma tissues. ERK signal pathway might play an important role in the initiation and development of the cervical carcinoma through c-fos protein, their cooperation might be one of the molecular mechanisms of cervical carcinoma.
Keywords/Search Tags:MAPK, ERK, PERK, c-fos, cervical carcinoma
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