ABSTRACT
OBJECTIVE: To investigate role of Zinc finger E-box binding homeobox 1 (ZEB1) in cervical cancer tissue (squamous cell carcinoma, SCC). DESIGN: Exploratory study. SETTING: University hospital. PATIENT(S): Sixty patients with SCC, including stage CINIII (n = 10), IB1 (n = 10), IB2 (n = 10), IIA1 (n = 10), IIA2 (n = 10), and IIB (n = 10) were studied. INTERVENTION(S): Caski cells were transfected with recombinant shZEB1 lentivirus or shCtrl lentivirus to generate stable ZEB1-knockdown Caski cells. MAIN OUTCOME MEASURE(S): ZEB1 expression was analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry in cervical cancer tissues. ZEB1 expression in Caski cells was down-regulated by short-hairpin RNA (shRNA) interference, and changes in ZEB1 expression corresponded with changes in the proliferation and migratory ability of Caski cells. RESULT(S): Quantitative real-time polymerase chain reaction and immunohistochemistry results revealed that ZEB1 expression and the ratio of Vimentin to E-cadherin were high in 27 of 50 SCC patients and correlated with advanced International Federation of Gynecology and Obstetrics stage, tumor size >4 cm, and parametrial invasion. However, the expression of ZEB1 in cervical cancer tissue was independent of age and SCC antigen level. Transfection of ZEB1 shRNA in Caski cells significantly decreased the messenger RNA and protein expression of ZEB1, parallel with increased expression of the epithelial marker E-cadherin and decreased expression of the mesenchymal marker Vimentin. Furthermore, the proliferation and migratory ability of Caski cells were significantly lower in the transfected group than in the nontransfected control group. CONCLUSION(S): Down-regulation of ZEB1 expression may protect the invasive front of the tumors from converting to a mesenchymal phenotype by reducing the proliferation and motility of cervical cancer cells, suggesting that ZEB1 might be a potential therapeutic target for SCC.
Subject(s)
Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/secondary , Epithelial-Mesenchymal Transition , Homeodomain Proteins/metabolism , Transcription Factors/metabolism , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/secondary , Aged , Carcinoma, Squamous Cell/pathology , Cell Movement , Cell Proliferation , Female , Humans , Middle Aged , Tumor Cells, Cultured , Uterine Cervical Neoplasms/pathology , Zinc Finger E-box-Binding Homeobox 1ABSTRACT
OBJECTIVE: To study the expression of matrix metalloproteinase-9(MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in ectopic and eutopic endometrium in patients with endometriosis. METHODS: The expressions of MMP-9 and TIMP-1 in ectopic and eutopic endometrium were detected by immunohistochemistry streptavidin-biotin peroxidase (SP) method in 45 patients with endometriosis (study group) and in 32 patients with uterine fibroid (control group). RESULTS: In the ectopic and eutopic endometrium of group and in the control group endometrium, the expression of MMP-9 was respectively 0.381, 0.336 and 0.276; the expression of TIMP-1 was respectively 0.239, 0.253, 0.267. As a result, the ratio of MMP-9/TIMP-1 in ectopic and eutopic endometrium of study group and in the control group endometrium was respectively 1.594, 1.293, 1.034. The difference of MMP-9, MMP-9/TIMP-1 in ectopic and eutopic and the control group endometrium was markedly significant (P < 0.01 or P < 0.05). The difference of the expression of TIMP-1 between ectopic and the control group endometrium was also markedly significant (P < 0.01). Higher expression of MMP-9 and lower expression of TIMP-1 in ectopic endometrium and higher expression of MMP-9 in eutopic endometrium occurred in the whole menses period, in which higher expression of MMP-9 in ectopic endometrium than in eutopic endometrium only took place in proliferative phase. CONCLUSION: The change of expression of MMP-9 and TIMP-1 in ectopic endometrium may be related to the pathogenesis of endometriosis.
