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Ribosomal S6 kinase 4 (RSK4) expression in ovarian tumors and its regulation by antineoplastic drugs in ovarian cancer cell lines

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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.

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Acknowledgments

This study was supported by a grant from the Fondo de Investigación en Salud, Instituto Mexicano del Seguro Social (FIS/IMSS/PROT/G10/855) to Dr. Laura Díaz-Cueto. Carlos Eduardo Perez-Juarez was a graduate student in the Programa de Maestria en Ciencias Biologicas at the Universidad Nacional Autonoma de Mexico. He was supported by a scholarship from the CONACYT (No. Becario: 245530) and the Instituto Mexicano del Seguro Social (Matricula: 99095927), Mexico.

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Authors and Affiliations

  1. 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

    Fabian Arechavaleta-Velasco, Aleida Olivares, Carlos Eduardo Perez-Juarez & Laura Diaz-Cueto

  2. 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

    Moises Zeferino-Toquero

  3. 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

    Isaias Estrada-Moscoso & Fazlollah Shahram Imani-Razavi

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  1. Fabian Arechavaleta-Velasco
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  2. Moises Zeferino-Toquero
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  5. Aleida Olivares
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  6. Carlos Eduardo Perez-Juarez
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  7. Laura Diaz-Cueto
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Correspondence to Laura Diaz-Cueto.

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Arechavaleta-Velasco, F., Zeferino-Toquero, M., Estrada-Moscoso, I. et al. Ribosomal S6 kinase 4 (RSK4) expression in ovarian tumors and its regulation by antineoplastic drugs in ovarian cancer cell lines. Med Oncol 33, 11 (2016). https://doi.org/10.1007/s12032-015-0724-6

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  • DOI: https://doi.org/10.1007/s12032-015-0724-6

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