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.

Ribosomal S6 protein kinase 4 promotes radioresistance in esophageal squamous cell carcinoma

“…However, the mRNA lev-because of their requirement for growth factors (16), indicating that RSK4 is functionally distinct from the other RSKs. Compared with the more in-depth research on the other RSKs in the field of cancer, there have been limited and conflicting reports describing the role of RSK4 in different cancer types (17)(18)(19)(20)(21)(22)(23)(24)(25). Using a tissue microarray (TMA) containing 20 kinds of human tumors and corresponding normal tissues, we found that RSK4 protein was highly expressed in renal cell carcinoma (RCC) and ESCC.…”

Aberrant expression of RSK4 in breast cancer and its role in the regulation of tumorigenicity

“…Among these, the X-linked ribosomal S6 kinase RPS6KA6 (RSK4) was first identified as a commonly deleted gene in complex X-linked mental retardation patients (4) and its ubiquitous expression in a number of cell types suggested its involvement in multiple biological and pathological processes such as murine embryogenesis, fibroblast growth and diabetes development (5)(6)(7)(8). RSK4 expression was found to be downregulated in several types of tumors such as colon carcinomas, renal cell carcinomas, colorectal adenomas, endometrial cancer and ovarian cancer (9)(10)(11). Furthermore, overexpression of RSK4 was found to induce cell cycle arrest and senescence features while RSK4 inhibition resulted in bypass of stress or oncogene-induced senescence, suggesting its function as a potential tumor-suppressor gene (9,12).…”

Integrated Analysis of Methylation-driven Genes and Pretreatment Prognostic Factors in Patients with Hepatocellular Carcinoma

“…RPS6KA6 plays a differential role in cancers and was reported to be an oncogene in lung squamous cell carcinoma and renal cell carcinoma [27,28]. In contrast, RPS6KA6 works as a tumor suppressor in endometrial cancer, acute myeloid leukemia, ovarian cancer, and breast cancer [29][30][31][32]. Furthermore, the low expression of RPS6KA6 was the result of DNA hypermethylation in endometrial cancers [29].…”