title: Misregulation of polo-like protein kinase 1, P53 and P21WAF1 in epithelial ovarian cancer suggests poor prognosis.
abstract: Polo-like protein kinase 1 (PLK1), P53 and P21WAF1 are relevant to cell cycle checkpoints and cancer biology. Misregulation of PLK1, P53 and P21WAF1 has been detected in several types of malignant tumors. The present study aimed to clarify the role of PLK1, P53 and P21WAF1 in the prognosis of ovarian cancer. PLK1 and P53 shRNA lentiviral plasmids were transfected into SK-OV-3 cells, respectively. Cell proliferation, apoptosis and invasion were examined by MTT assay, flow cytometry and Matrigel assay, respectively. Survival time of the animals was observed in a xenograft model. Expression levels of PLK1, P53 and P21WAF1 were detected in different ovarian tissues by immunohistochemistry and western blot analysis. Their correlations to the clinicopathologic characteristics of the epithelial ovarian cancer (EOC) cases and their interrelationships were analyzed. Risk factors of prognosis for EOC were determined by logistic regression analysis. The survival time of EOC patients was measured by Kaplan-Meier analysis. After PLK1 or P53 knockdown, proliferation of the SK-OV-3 cells was inhibited, the apoptosis rate was increased, and cell invasion was suppressed in vitro, and the survival time was prolonged in the animals. Expression levels of P53, p-P53 (Ser15), P21WAF1, growth arrest and DNA damage‑inducible gene 45 (GADD45) and 14-3-3σ were upregulated in the SK-OV-3 cells after PLK1 knockdown, but downregulated after P53 knockdown. Higher expression levels of PLK1 and P53 were observed in patients with a higher FIGO stage and worse histological differentiation, but lower P21WAF1 was noted at a higher FIGO stage. Negative correlations were observed between expression of PLK1 and P53 and P53 and P21WAF1 in the EOC cases. PLK1, P53 and P21WAF1 could be used to assess the prognosis of EOC, respectively, but only PLK1 was found to be an independent prognostic factor. The overall survival time of subjects exhibiting PLK1-positive/P53-positive expression and PLK1-positive/P21WAF1-negative expression was obviously shorter than the other patient groups at the end of the follow-up. These results indicate that PLK1 is implicated in ovarian carcinogenesis and may owe its ability to inhibition of the activity of P53. In addition, misregulation of PLK1 coincident with P53 and P21WAF1 in EOC suggests poor prognosis.
authors.affiliation: Department of Gynaecology, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Ruitao
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Gynaecology, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Huirong
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Gynaecology, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Ren
authors.affiliation: Department of Gynaecology, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Huina
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Gynaecology, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Gynaecology, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Youxing
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Gynaecology, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
mesh_terms: D048948:14-3-3 Proteins / Q000096:biosynthesis; D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D000077216:Carcinoma, Ovarian Epithelial; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005095:Exoribonucleases / Q000096:biosynthesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009687:Nuclear Proteins / Q000096:biosynthesis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult; D000097869:Polo-Like Kinase 1; D000097642:GADD45 Proteins
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005095:Exoribonucleases; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D000097869:Polo-Like Kinase 1; C493956:CDKN1A protein, human; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C413442:SFN protein, human