The Correlation Research Of GRP94in Human Cervical Carcinoma

Background Worldwide, cervical cancer is the second most common cancer inwomen. About500,000new cases and more than250,000deaths occur annually. Indeveloping countries, where more than80%of the cases occur, the incidence may be ashigh as80/100,000. The majority are squamous cell carcinoma and adenocarcinoma,while other types are much less common. Cervical cancers are attributed to infectionwith the human papillomavirus and about70%of them are caused by types16and18.They are preceded by cervical intraepithelial neoplasia, mainly its immediate precursorCIN3. While HPV is a necessary cause of cervical cancer, other cofactors are necessaryfor progression from cervical HPV infection to cancer. These cofactors includelong-term use of hormonal contraceptives, high parity, tobacco smoking, andco-infection with human immunodeficiency virus. Additional probable cofactors areco-infection with herpes simplex virus type2and Chlamydia trachomatis,immunosuppression, certain dietary deficiencies, and genetic and immunological hostfactors. Cervical cytological screening may lead to diagnosis of the precursor lesions,which can be treated very successfully.Glucose regulated protein94is a member of heat shock protein family, whichresides in the endoplasmic reticulum(ER) is highly conserved. GRP94plays animportant role in folding, transporting, secretion and degradation of ER proteins. It canalso binding with calcium in the ER, mediating the immunogenicity of virus-infectedcells and tumor cells. Lots of articles show that, GRP94is overexpressed in breastcancer, colon cancer, stomach cancer and other tumor cells and tumor cell lines. The expression of GRP94is associated with the differentiation and progression of tumor.The lower tumor differentiation, the higher GRP94’s expression. The higher tumorprogression, the higher expression of GRP94. Blood vessel poorly formatted in solidtumor which cause glucose starvation, hypoxia, acidosis and accumulation of numerousmisfolded and unfolded proteins. The large amount of GRP94expression are inducedby unfolded protein response. GRP94promote the proliferation of tumor cells and thegeneration of tumor blood vessels.Objectives To investigate the significance of the difference of the expression anddistribution of GRP94between normal cervical tissue and cervical cancer. This studywill provide a theoretical basis and treatment of clues.Methods①Analysis of Mass Spectrometry showing the mainly different proteinbetween normal cervical tissue and cervical cancer;②R T-PCR detection of theexpression of GRP94in cervical cancer;③Western Blot detection of the expression ofGRP94in cervical cancer;④Immunohistochemical detection of the expression ofGRP94in cervical cancer and normal cervical tissue;⑤Immunohistochemical detectionof the expression of GRP94in normal cervical exfoliated cells and low-grade squamousintraepithelial lesions in cervical exfoliated cells.Results①Analysis of Mass Spectrometry show GRP94is the mainly differentprotein between normal cervical tissue and cervical cancer;②R T-PCR detection of theexpression of GRP94in cervical cancer is much higher than those in normal cervicaltissue, There is a significantly difference between two groups (p<0.05);③Western Blotdetection of the expression of GRP94in cervical cancer is much higher than those innormal cervical tissue, There is a significantly difference between two groups(p<0.05);④Western Blot detection of the expression of GRP94in cervical cancer cell lines are higher than those in normal cervical tissue, There is a significantly differencebetween two groups (p<0.05);⑤Immunohistochemical detection of the expression ofGRP94in cervical cancer is much higher than those in normal cervicaltissue;⑥Immunohistochemical detection of the expression of GRP94in LISLcervicalexfoliated cells is much higher than those in normal cervical exfoliated cells. It alsopresents a tendency to cell membrane.Conclusion GRP94is the main different protein between normal cervical tissue andcervical cancer. The expression of GRP94in cervical cancer is higher than in normalcervical tissue. The expression of GRP94in LISL cervical exfoliated cells is muchhigher than in normal cervical exfoliated cells, and it presents a tendency to cellmembrane.