title: Ribosomal S6 kinase 4 (RSK4) expression in ovarian tumors and its regulation by antineoplastic drugs in ovarian cancer cell lines.
abstract: Survival rate in ovarian cancer depends on the stage of the disease. RSK4, which has been considered as a tumor suppressor factor, controls cells invasion due to its antiinvasive and antimetastatic properties. Modulation of RSK4 expression could be an important event to increase the survival rate in ovarian cancer patients. Thus, the goal of the present study was to establish the differences in RSK4 expression among normal, benign and malignant ovarian tissues and to determine whether antineoplastic drugs regulate its expression in SKOV3 and TOV-112D cells. RSK4 levels in 30 malignant ovarian tumors, 64 benign tumors and 36 normal ovary tissues were determined by reverse transcription polymerase chain reaction and Western blot. Modulation of RSK4 expression by two antineoplastic drugs (cisplatin and vorinostat) was also studied in the SKOV3 and TOV-112D ovarian cancer cell lines using the same techniques. RSK4 mRNA and protein levels were decreased in malignant ovarian tumors as compared to benign tumors and normal tissue. These low-RSK4 levels were significantly associated with advanced stages of ovarian cancer. RSK4 expression was increased after incubation of SKOV3 and TOV-112D cell lines with cisplatin and vorinostat for 24 h. The combination of these antineoplastic drugs did not produce a synergistic or additive effect. These results suggest that RSK4 is expressed at low levels in malignant ovarian tumors, which correlates with advanced stages of the disease. Additionally, RSK4 expression is regulated by cisplatin and vorinostat in two ovarian cancer cell lines.
authors.affiliation: Research Unit in Reproductive Medicine, UMAE Hospital de Gineco Obstetricia No. 4 "Luis Castelazo Ayala", IMSS, Av. Rio Magdalena No. 289, Sexto piso. Tizapán, San Angel, 01090, Mexico, DF, Mexico.
authors.forename: Fabian
authors.initials: F
authors.lastname: Arechavaleta-Velasco
authors.affiliation: Department of Gynecological Oncology, UMAE Hospital de Gineco Obstetricia No. 4 "Luis Castelazo Ayala", IMSS, Av. Rio Magdalena No. 289, Sexto piso. Tizapán, San Angel, 01090, Mexico, DF, Mexico.
authors.forename: Moises
authors.initials: M
authors.lastname: Zeferino-Toquero
authors.affiliation: Department of Pathology, UMAE Hospital de Gineco Obstetricia No. 4 "Luis Castelazo Ayala", IMSS, Av. Rio Magdalena No. 289, Sexto piso. Tizapán, San Angel, 01090, Mexico, DF, Mexico.
authors.forename: Isaias
authors.initials: I
authors.lastname: Estrada-Moscoso
authors.affiliation: Department of Pathology, UMAE Hospital de Gineco Obstetricia No. 4 "Luis Castelazo Ayala", IMSS, Av. Rio Magdalena No. 289, Sexto piso. Tizapán, San Angel, 01090, Mexico, DF, Mexico.
authors.forename: Fazlollah Shahram
authors.initials: FS
authors.lastname: Imani-Razavi
authors.affiliation: Research Unit in Reproductive Medicine, UMAE Hospital de Gineco Obstetricia No. 4 "Luis Castelazo Ayala", IMSS, Av. Rio Magdalena No. 289, Sexto piso. Tizapán, San Angel, 01090, Mexico, DF, Mexico.
authors.forename: Aleida
authors.initials: A
authors.lastname: Olivares
authors.affiliation: Research Unit in Reproductive Medicine, UMAE Hospital de Gineco Obstetricia No. 4 "Luis Castelazo Ayala", IMSS, Av. Rio Magdalena No. 289, Sexto piso. Tizapán, San Angel, 01090, Mexico, DF, Mexico.
authors.forename: Carlos Eduardo
authors.initials: CE
authors.lastname: Perez-Juarez
authors.affiliation: Research Unit in Reproductive Medicine, UMAE Hospital de Gineco Obstetricia No. 4 "Luis Castelazo Ayala", IMSS, Av. Rio Magdalena No. 289, Sexto piso. Tizapán, San Angel, 01090, Mexico, DF, Mexico. ldiazcueto@gmail.com.
authors.forename: Laura
authors.identifier: http://orcid.org/0000-0002-2270-3140
authors.initials: L
authors.lastname: Diaz-Cueto
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D010053:Ovary / Q000201:enzymology; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics* / Q000378:metabolism; D000077337:Vorinostat
chemical_list: D006877:Hydroxamic Acids; D000077337:Vorinostat; C501305:RPS6KA6 protein, human; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D002945:Cisplatin
keywords: Cisplatin; Ovarian cancer; RPS6KA6; RSK4; Ribosomal S6 kinase 4; Vorinostat