title: The roles of parafibromin expression in ovarian epithelial carcinomas: a marker for differentiation and prognosis and a target for gene therapy.
abstract: Parafibromin is a protein encoded by hyperparathyroidism 2 (HRPT2) and its downregulated expression is involved in the pathogenesis of parathyroid, breast, gastric, colorectal, lung, head and neck cancers. We aimed to investigate the roles of parafibromin expression in tumorigenesis, progression, or prognostic evaluation of ovarian cancers. HRPT2-expressing plasmid was transfected into ovarian cancer cells with the phenotypes and related molecules examined. The messenger RNA (mRNA) and protein expression of parafibromin were also examined in ovarian normal tissue, benign and borderline tumors and cancers by reverse transcription-polymerase chain reaction (RT-PCR), Western blot, or immunohistochemistry respectively. It was found that parafibromin overexpression caused a lower growth, migration and invasion, higher sensitivity to cisplatin and apoptosis than the mock and control (P < 0.05). The transfectants showed the hypoexpression of phosphoinositide 3-kinase (PI3K), Akt, p70 ribosomal protein S6 kinase (p70s6k), Wnt5a, B cell lymphoma-extra large (Bcl-xL), survivin, vascular endothelial growth factor (VEGF) and matrix metallopeptidase 9 (MMP-9) than the mock and control at both mRNA and protein levels (P < 0.05). According to real-time PCR, parafibromin mRNA level was lower in ovarian benign tumors and cancers than normal ovary (P < 0.05), while parafibromin was strongly expressed in metastatic cancers in omentum than primary cancers by Western blot. Immunohistochemically, parafibromin expression was stronger in primary cancers than that in ovarian normal tissue (P < 0.05) but weaker than the metastatic cancers (P < 0.05) with a positive correlation with dedifferentiation, ki-67 expression and the lower cumulative survival rate (P < 0.05). These findings indicate that parafibromin downregulation might promote the pathogenesis, dedifferentiation and metastasis of ovarian cancers possibly by suppressing aggressive phenotypes, such as proliferation, cell cycle, apoptosis, migration and invasion.
authors.affiliation: Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, 121001, China.
authors.forename: Dao-Fu
authors.initials: DF
authors.lastname: Shen
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, 121001, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, 121001, China.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Yang
authors.affiliation: Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, 121001, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Fang
authors.affiliation: Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, 121001, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, 121001, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, 121001, China.
authors.forename: Ji-Cheng
authors.initials: JC
authors.lastname: Wu
authors.affiliation: Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, 121001, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Shi
authors.affiliation: Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, 121001, China.
authors.forename: Jun-Jun
authors.initials: JJ
authors.lastname: Li
authors.affiliation: Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, 121001, China.
authors.forename: Xiang-Xuan
authors.initials: XX
authors.lastname: Zhao
authors.affiliation: Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, 121001, China.
authors.forename: Wen-Feng
authors.initials: WF
authors.lastname: Gou
authors.affiliation: Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, 121001, China. zheng_huachuan@hotmail.com.
authors.forename: Hua-Chuan
authors.initials: HC
authors.lastname: Zheng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor; D000077216:Carcinoma, Ovarian Epithelial; D002454:Cell Differentiation; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000473:pathology* / Q000628:therapy; D010051:Ovarian Neoplasms / Q000473:pathology* / Q000628:therapy; D011379:Prognosis; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*
chemical_list: D014408:Biomarkers, Tumor; C454900:CDC73 protein, human; D025521:Tumor Suppressor Proteins
keywords: Gene therapy; Ovarian cancer; Parafibromin; Pathogenesis; Progression