In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 4303-4303
Abstract:
Abstract Background and Purpose-Ovarian cancer is the most lethal gynecological malignancy in women, but the essential mechanism remains unclear. Studies have shown that many ribosomal proteins are dysfunctional in various tumors. The small ribosomal protein subunit S7 (RPS7) has been reported to interact with MDM2 and may function as a tumor suppressor, but its role in cancer development is largely unknown. Here, we examined the molecular function of RPS7 in human ovarian cancer. Experimental Design-Retrovirus-mediated small hairpin RNA (shRNA) was used to silence the expression of RPS7 in ovarian cancer cell lines SKOV3 and OVCA433, named SKOV3-RPS7i, OVCA433-RPS7i plus their GFP shRNA (GFPi) controls. Cell proliferation, cell cycle, apoptosis, cell migration and invasion, and tumor growth were tested to determine the function of RPS7 in ovarian cancer. Results-Immunostaining of RPS7 showed that RPS7 was higher in ovarian cancer tissues than in nomal tissues. Silencing of RPS7 in SKOV3 and OVCA433 cells promoted cell growth and markedly enhanced anchorage-independent colony formation. Depletion of RPS7 accelerated cell cycle progression through G1-S transition, which was evidenced by alterations of cell cycle regulatory proteins including p21waf1/cip1, CDK2/4, Cyclin B1, and Cyclin D1. Knockdown of RPS7 weakened cell apoptosis by increasing the expression of anti-apoptotic proteins including BCL2 and BCL-XL, and decreasing the expression of apoptotic molecules including p27cip/kip, BAK, and BAD. However, knockdown of RPS7 reduced cell migration and invasion. Further analysis showed that the expression of β-catenin, MMP2, and MMP13 was decreased, but E-cadherin was increased in RPS7-silenced cells compared with in controls, indicating that RPS7 is associated with metastasis. Moreover, P85α, P110α and AKT1/2 were decreased in SKOV3-RPS7i and OVCA433-RPS7i, suggesting that RPS7 functions through PI3K/AKT signal pathway. Although the basal levels of ERK 1/2, MEK1/2, and p38 were inconsistently altered, but the phosphorylation of MEK1/2 (Ser217/221), ERK1/2 (Thr202/Tyr204), and p38 (Thr180/Tyr182) was reduced in SKOV3-RPS7i and OVCA433-RPS7i cells, compared with in controls. Thus, our results suggested that RPS7 appears to regulate cell proliferation, apoptosis, and tumorigenesis through PI3K/AKT and MAPK signal pathways. Conclusion-RPS7 may function as an anti-tumor factor in ovarian tumorigenesis through PI3K/AKT and MAPK signal pathways. Citation Format: Ziliang Wang, Lili Lu, Jianmin Sun, Jiao Meng, Wen Gao, Yan Wang, Huizhen Sun, Jin Hou, Hongyu Gu, Zhen Wang, Yuhu Xin, Gong Yang. The Small Ribosomal Protein Subunit S7 Functions as a Tumor Suppressor to regulate ovarian tumorigenesis through PI3K/AKT and MAPK pathways. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4303. doi:10.1158/1538-7445.AM2013-4303
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2013-4303
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2013
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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