title: Expression of peptidylarginine deiminase type 4 in ovarian tumors.
abstract: Peptidylarginine deiminase type 4 (PADI4) converts arginine residues into citrulline. The current study focused on the expression of PADI4 in various subtypes of ovary cancers, and this study investigated the effects of estrogen on PADI4 expression in SKOV-3 cells that originated from ovary tumors. We utilized immunohistochemistry, real-time PCR and western blotting to analyze the expression of PADI4 in the tumor tissues and in the cell line that were cultured with estrodial-17β. PADI4 was detected in serious cystadenocarcinoma (n=39, positivity=100%), clear cell cancer (n=7, positivity= 100%), mucinous cystadenocarcinoma (n=6, positivity=100%), dysgerminoma (n=6, positivity=100%), squamous cell tumor (n=6, positivity=100%), sibnet-ring cell carcinoma (n=6, positivity=100%), endodermal sinus tumor (n=6, positivity=100%), germ cell tumors (n=6, positivity=100%) and immature teratoma (n=6, positivity=100%). However, PADI4 was either not detected or detected at low levels in granulosa cell tumor (n=6), malignant thecoma (n=6), ovarian cystadenoma (n=5) and normal ovarian tissue (n=11). For serious cystadenocarcinoma, all of the samples with high PADI4 expression belonged to the T1 and T2 stages of pTMN, whereas all of the samples that exhibited weak or moderate PADI4 expression belonged to the T3 and T4 stages. PADI4 was evenly distributed in the cytoplasm of tumor cells of serious cystadenocarcinoma that were classified as being grade II and III by histopathological scoring. However, PADI4 showed granular cellular distribution in the tumor tissues that were isolated from grade I cystadenocarcinoma. In addition, the PADI4 level was positively related with the ages of the patients that presented with serious adenocarcinoma (p=0.029). Real-time PCR and western blot analyses confirmed that PADI4 was expressed at higher levels in ovarian adenocarcinoma (n=8) compared to ovarian cystadenoma (n=5) (p< 0.05). The study also detected an increased level of PADI4 in SKOV-3 cells that were incubated with estrodial-17β in the range of 10(-12) to 10(-4)M. The results suggest an important role for PADI4 in the tumorigenesis of ovary cancers that are under the regulation of estrogen.
authors.affiliation: Research Center for Medicinal Biotechnology, Shandong Academy of Medicinal Sciences. Key Laboratory for Biotech-Drugs Ministry of Health & Provincial Laboratory for Modern Medicine and Technology of Shandong, Jinan, Shandong 250062, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Chang
authors.forename: Guangying
authors.initials: G
authors.lastname: Yuan
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Wang
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006867:Hydrolases / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D010051:Ovarian Neoplasms / Q000201:enzymology*; D016133:Polymerase Chain Reaction; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D004958:Estradiol; D006867:Hydrolases; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases
references.citation: Biochem Biophys Res Commun. 2002 Jan 25;290(3):979-83
references.pmid: 11798170
references.citation: Mol Carcinog. 2006 Mar;45(3):183-96
references.pmid: 16355400
references.citation: J Biol Chem. 2008 Jul 18;283(29):20060-8
references.pmid: 18499678
references.citation: Acta Radiol Oncol. 1980;19(4):241-4
references.pmid: 6257044
references.citation: Oncologist. 2002;7(1):73-81
references.pmid: 11854549
references.citation: Gynecol Oncol. 2007 Nov;107(2):266-73
references.pmid: 17698176
references.citation: Hum Reprod Update. 2007 Sep-Oct;13(5):453-63
references.pmid: 17573406
references.citation: Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10746-50
references.pmid: 9724775
references.citation: Mol Endocrinol. 2007 Jul;21(7):1617-29
references.pmid: 17456793
references.citation: Cancer Surv. 1994;19-20:287-307
references.pmid: 7895220
references.citation: Clin Endocrinol (Oxf). 1998 Dec;49(6):695-707
references.pmid: 10209555
references.citation: J Leukoc Biol. 2001 Jul;70(1):46-51
references.pmid: 11435484
references.citation: Apoptosis. 2006 Feb;11(2):183-96
references.pmid: 16502257
references.citation: J Clin Oncol. 2003 Mar 15;21(6):1180-9
references.pmid: 12637488
references.citation: Cell. 2004 Sep 3;118(5):545-53
references.pmid: 15339660
references.citation: Endocrine. 2005 Apr;26(3):297-300
references.pmid: 16034185
references.citation: Int Immunol. 1998 Dec;10(12):1891-5
references.pmid: 9885910
references.citation: Ann Rheum Dis. 2004 Apr;63(4):373-81
references.pmid: 15020330
references.citation: Am J Epidemiol. 1995 May 1;141(9):828-35
references.pmid: 7717359
references.citation: Nucleic Acids Res. 2001 May 1;29(9):e45
references.pmid: 11328886
references.citation: J Biol Chem. 2002 Dec 20;277(51):49562-8
references.pmid: 12393868
references.citation: BMC Cancer. 2009 Jan 30;9:40
references.pmid: 19183436
references.citation: Science. 2004 Oct 8;306(5694):279-83
references.pmid: 15345777
references.citation: Endocr Rev. 1998 Aug;19(4):397-428
references.pmid: 9715373
references.citation: Rheumatology (Oxford). 2005 Jan;44(1):40-50
references.pmid: 15466895