title: Regulatory role of osteopontin in malignant transformation of endometrial cancer.
abstract: Osteopontin (OPN) involves in the tumor-promoting or metastasis in human endometrial cancer. Depletion of OPN gene expression in endometrial cancer cells was significantly decreased in cell viability and the cells undergo apoptotic cell death. The status of OPN in THESC, RL95, Hec1A and Ishikawa cell lines were analyzed by RT-PCR and western blot. After OPN-siRNA transfection, mRNA and protein expression levels of OPN were determined in Hec1A and Ishikawa cells. Cell proliferation and cell cycle distribution were observed by MTT and flow cytometry analysis. DNA fragmentation assay was used to measure cell apoptosis. Cell migration was assessed by wound healing assay. Depletion of OPN gene expression in endometrial cancer cell lines (Hec1A and Ishikawa cells) reproducibly changed their ability of proliferation. Concomitant changes were seen in the expression of OPN binding cell surface receptors, cell cycle-regulatory genes, cell invasion and colony formation nature of the tumor cells. Decreased colonizing potential in the absence of OPN was reversed in the presence of recombinant OPN. Inhibition of anchorage-independent growth was observed in the presence of metabolic inhibitors of the PI3K, Src and integrin signaling cascades, which was ameliorated in the presence of exogenously added OPN. Our result showed the role of OPN in endometrial cancer, in particular on the malignancy-promoting aspects of OPN that may pave way for new approaches to the clinical management of endometrial cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Keimyung University School of Medicine, 56 Dalseong-ro, Jung-gu, Daegu 700-712, South Korea.
authors.forename: Sabarish
authors.initials: S
authors.lastname: Ramachandran
authors.forename: Kun-Young
authors.initials: KY
authors.lastname: Kwon
authors.forename: So-Jin
authors.initials: SJ
authors.lastname: Shin
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Kwon
authors.forename: Soon-Do
authors.initials: SD
authors.lastname: Cha
authors.forename: Hyun-Gyo
authors.initials: HG
authors.lastname: Lee
authors.forename: Young-Bin
authors.initials: YB
authors.lastname: Hong
authors.forename: Insoo
authors.initials: I
authors.lastname: Bae
authors.forename: Gun-Ho
authors.initials: GH
authors.lastname: Lee
authors.forename: Chi-Heum
authors.initials: CH
authors.lastname: Cho
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009362:Neoplasm Metastasis / Q000235:genetics; D053495:Osteopontin / Q000235:genetics* / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D053495:Osteopontin