title: [Effect of extracellular signal-regulated kinas 1/2 expression and HPV16 infection and their interaction in progression of cervical cancerization].
abstract: Objective:To investigate the effect of ERK1/2 protein expression and HPV16 infection, as well as their interaction in the cervical carcinogenesis.Methods:A total of 176 patients, including 34 cases with normal cervix (NC), 26 cases with cervical intraepithelial neoplasm Ⅰ (CIN Ⅰ), 57 cases with cervical intraepithelial neoplasm Ⅱ/Ⅲ (CIN Ⅱ/Ⅲ) and 59 cases with cervical squamous cell carcinoma (SCC), were enrolled from Shanxi Tumor Hospital, Shanxi Maternal and Child Health Center, Jincheng Coal General Hospital from September 2013 to March 2014. The information about their demographic characteristics and risk factors associated with cervical cancer was collected with structural questionnaire, and cervical tissue samples were collected from each subject. HPV16 infection was detected by PCR, and phosphorylation of ERK1/2 (p-ERK1/2) protein expression levels were detected by immunohistochemistry. Meanwhile, cervical cancer cell lines Siha (HPV16 positive) and C33A (HPV negative) were treated with ERK inhibitor U0126 in vitro. Cell proliferation was determined by living cell count, cell cycle and apoptosis was detected by flow cytometry.Results:The HPV16 infection rate (trendχ(2)=17.99,P<0.001) and p-ERK1/2 protein high expression (trendχ(2)=10.58,P=0.001) increased gradually along with the severity of cervix lesions. There was an additive interaction between HPV16 infection and p-ERK protein expression in the CIN Ⅰ, CIN Ⅱ/Ⅲ and SCC groups. Cell experiments showed that after ERK inhibition, the proliferation of the two cells were reduced (Siha:t=6.863,P<0.001; C33A:t=7.092,P<0.001) and the apoptosis were increased (Siha:t=-5.201,P=0.006; C33A:t=-4.335,P=0.005). After ERK inhibition, the cell proliferation index of Siha (HPV16 positive) was higher than that of C33A (HPV16 negative) (t=7.066,P<0.001), but the apoptosis rate of Siha was lower than that of C33A (t=-2.431,P=0.057).Conclusions:HPV16 infection and the high expression of p-ERK1/2 could increase the risk of cervical cancer. And there might be synergistic actions between the two factors in the progression of cervical cancer. The effect of ERK1/2 activation to HPV16 infection cells might be more significant in the process of cervical cancer cell proliferation and apoptosis.
authors.affiliation: Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: S L
authors.initials: SL
authors.lastname: Fan
authors.affiliation: Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: L
authors.initials: L
authors.lastname: Ding
authors.affiliation: Community Health Centre, Shanxi Cardiovascular Hospital, Taiyuan 030001, China.
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Ren
authors.affiliation: Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: X S
authors.initials: XS
authors.lastname: Sun
authors.affiliation: Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: C C
authors.initials: CC
authors.lastname: Li
authors.affiliation: Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: C L
authors.initials: CL
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: W L
authors.initials: WL
authors.lastname: Jia
authors.affiliation: Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Q L
authors.initials: QL
authors.lastname: Li
authors.affiliation: Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: J T
authors.initials: JT
authors.lastname: Wang
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D052162:Human papillomavirus 16; D006801:Humans; D007150:Immunohistochemistry; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics*; D030361:Papillomavirus Infections; D016133:Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000378:metabolism / Q000821:virology*
chemical_list: C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1
keywords: Cervical carcinogenesis; ERK1/2; HPV16; Interaction