A Study On The Relationship Of FHIT Protein And HPV₁₆E₆,HPV₁₆E₇ Oncoprotein In Cervical Carcinoma

Objective: To determine the relationship of FHTT gene expression and oncogene expression in cervical carcinomaMethods: Immunohistochemistry were used to detect the expression of FHTT gene, HPV₁₆E₆ and HPV₁₆E₇ gene in 15 normal cervices and 25 CINs as well as 61 primary invasive cervical carcinomas;Immunofluorecence and flow cytometry(FCM) were used to detect the expression of FHTT protein and HPV₁₆E₆/E₇ oncoproteins in CasKi and SiHa cervical cancer cell lines;To see the changing of FHTT expression after the HPV₁₆E₆ expression were suppressed by HPV₁₆E₆ SiRNA transduction in CasKi cell line.Results: 1.FHTT protein was expressed moderately or strongly in all 15/15(100%)normal cervices,in contrast,loss or reduced expression of FHTT protein was observed in 4/14(28.57%)CINI-II 7/11(63.64%) ON III and in 52/61(85.25%) invasive cervical cancers.(l)The impaired FHTT expression indicated the degree of pathological changes of cervix(P<0.05).(2)The impaired FHTT expression was notcorrelated with the histological grade -. the clinical stage and the lymph node metastasis of cervical carcinoma(P>0.05).2. HPV16E6 protein was not expressed in all 15 normal cervices. HPV16E6 protein was expressed in 1/14(7.14%) CINI-EU 4/11(36.36%) ON m and in 35/61(57.38%) invasive cervical cancers.The expression of HPVi6E<; oncoprotein were higher in ON HI and in invasive cervical cancers than that in normal cervices and QNI-II(P<0.05).The expression of HPVieEg oncoprotein was correlated with the histological grade of cervical carcinoma(P<0.05) but not correlated with the clinical stage and lymph node metastasis(P>0.05).3.The expression of HPV16E7 was not correlated with the degree of pathological changes of cervix^ the histological grade> the clinical stage and the lymph node metastasis of cervical carcinoma(P>0.05).4.There is a relationship between the expression of HPVi6Ee oncoprotein and FHTT protein(P<0.0Us= - 0.449).HPV]6E7 has no relationship with FfflT expression (PX).O5).5.1n CasKk SiHa cervical cancer cell lines,the FHTT protein level are 73.50± 5.65 > 53.10 + 4.17 separately; HPVisEe level are 20.73 ± 6.35 > 1.77±0.25 separately;HPV]6E7 level are 56.80±4.30 > 49.27±8.06 separately.There is no significant difference of HPVi6E7 expression between the two cell lines(P>0.05).The FHIt level and HPV16E6 level are significantly lower in SiHa cell line than in CasKicell line(P<0.05).6.Before and after HPVujEe SiRNA transduction,tiie FHTT level in CasKi cell line are 73.5+5.65, 109.9+5.09 separately; theHPVieEe level are 20.73+6.35? 8.27+1.05 separately (P<0.05) . FHTT protein level was elevated with the suppression of HPVieEg by HPV16JE6 SiRNA transduction in CasKi cell line. Conclusion: 1. The expression of HPV16E6 and HPVi^E? oncoprotein in cervical carcinoma are not parallel. HPV16E7 might related to the early stage of cervical carcinogenisis;HPVi6E6 might related to the later stage of cervical carcinogenisis. HPV16E6 detection seems to be a more valuable indicator of malignant changing in premalignant cervical lesion.2. HPV16E6 protein is able to regulate the expression of FHTT protein inversely. HPV infection is a crucial factor of cervical carcinogenisis.