title: A candidate tumor suppressor HtrA1 is downregulated in ovarian cancer.
abstract: We report here that HtrA1, a candidate tumor suppressor, is downregulated in ovarian cancer. Expression of HtrA1 is downregulated in five of seven ovarian cancer cell lines. In total, 59% of primary ovarian tumors have either a complete absence or markedly reduced levels of HtrA1 expression compared to the brushings of ovarian surface epithelium. Primary ovarian tumors show high frequencies of loss of an allele at microsatellite markers near htrA1 locus on 10q26. Downregulation of HtrA1 in SKOV3 by antisense transfection promotes anchorage-independent growth, while exogenous expression of HtrA1 in OV202 induces cell death. HtrA1-induced cell death is not inhibited by the broad caspase inhibitor, zVAD(OMe)fmk, but instead reflects serine protease activity associated with HtrA1. These observations raise the possibility of HtrA1 as a candidate tumor suppressor involved in promoting serine-protease-mediated cell death and that downregulation of HtrA1 in ovarian cancer may contribute to malignant phenotype.
authors.affiliation: Mayo Clinic Cancer Center and Department of Experimental Pathology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Chien
authors.forename: Julie
authors.initials: J
authors.lastname: Staub
authors.forename: Shou-Ih
authors.initials: SI
authors.lastname: Hu
authors.forename: Michele R
authors.initials: MR
authors.lastname: Erickson-Johnson
authors.forename: Fergus J
authors.initials: FJ
authors.lastname: Couch
authors.forename: David I
authors.initials: DI
authors.lastname: Smith
authors.forename: Robert M
authors.initials: RM
authors.lastname: Crowl
authors.forename: Scott H
authors.initials: SH
authors.lastname: Kaufmann
authors.forename: Viji
authors.initials: V
authors.lastname: Shridhar
mesh_terms: D017209:Apoptosis; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D002879:Chromosomes, Human, Pair 10; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism
chemical_list: D005819:Genetic Markers; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases