Browse > Article
http://dx.doi.org/10.7314/APJCP.2014.15.14.5917

RASSF1A Suppresses Proliferation of Cervical Cancer Cells  

Feng, Lei (Department of Gynecology and Obstetrics, People's Hospital of Pingyi County)
Li, Jie (Department of Thoracic Surgery, Chinese PLA General Hospital)
Yan, Ling-Di (Beijing Institute of Pharmacology and Toxicology)
Tang, Jian (Department of Cardio-thoracic Surgery, First Affiliated Hospital of Chinese PLA General Hospital)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.14, 2014 , pp. 5917-5920 More about this Journal
Abstract
Background: This study aimed to explore the effects of ras association domain family 1 A (RASSF1A) on proliferation and apoptosis of human cervical cancer cell line Hela cells. Materials and Methods: RASSF1A was cloned into the pcDNA3.1(+) vector to generate pcDNA3.1(+)-RASSF1A plasmid for transfection into Hela cells. Changes in the proliferation and apoptosis of cultured Hela cells were examined by the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium chloride assay and flow cytometry. A protein array was used to analyze the expression of apoptotic factors. Results: Plasmid pcDNA3.1(+)-RASSF1A was generated and transfected into Hela cells to stably express RASSF1A in Hela cells. RASSF1A transfection was effective in inhibiting the proliferation of Hela cells up to 52.4%, as compared to cells transfected with an empty plasmid. RASSF1A expression also successfully induced apoptosis in human cervical cells with an apoptosis rate of 20.5%. More importantly, protein array results showed that RASSF1 A transfection induced overexpression of p21 and caspase 8, while decreasing the expression of survivin in Hela cells. Conclusions: RASSF1A expression was effective in suppressing the proliferation and increasing apoptosis of Hela cells, and may be a potential therapy for cervical cancer in clinic.
Keywords
RASSF1A; cervical cancer; Hela cell; proliferation; apoptosis;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Srivastava A K, Singh P K, Srivastava K, et al (2013). Diagnostic role of survivin in urinary bladder cancer. Asian Pac J Cancer Prev, 14, 81-5.   과학기술학회마을   DOI   ScienceOn
2 van der Weyden L, Tachibana K K, Gonzalez M A, et al (2005). The RASSF1A isoform of RASSF1 promotes microtubule stability and suppresses tumorigenesis. Mol Cell Biol, 25, 8356-67.   DOI
3 Vos M D, Dallol A, Eckfeld K, et al (2006). The RASSF1A tumor suppressor activates Bax via MOAP-1. J Biol Chem, 281, 4557-63.   DOI
4 Walboomers J M, Jacobs M V, Manos M M, et al (1999). Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol, 189, 12-9.   DOI
5 Abiramasundari G, Sumalatha K R, Sreepriya M (2012). Effects of Tinospora cordifolia (Menispermaceae) on the proliferation, osteogenic differentiation and mineralization of osteoblast model systems in vitro. J Ethnopharmacol, 141, 474-80.
6 Baksh S, Tommasi S, Fenton S, et al (2005). The tumor suppressor RASSF1A and MAP-1 link death receptor signaling to Bax conformational change and cell death. Mol Cell, 18, 637-50.   DOI
7 Agathanggelou A, Bieche I, Ahmed-Choudhury J, et al (2003). Identification of novel gene expression targets for the Ras association domain family 1 (RASSF1A) tumor suppressor gene in non-small cell lung cancer and neuroblastoma. Cancer Res, 63, 5344-51.
8 Agathanggelou A, Cooper W N , Latif F (2005). Role of the Ras-association domain family 1 tumor suppressor gene in human cancers. Cancer Res, 65, 3497-508.   DOI   ScienceOn
9 Ahmed-Choudhury J, Agathanggelou A, Fenton S L, et al (2005). Transcriptional regulation of cyclin A2 by RASSF1A through the enhanced binding of p120E4F to the cyclin A2 promoter. Cancer Res, 65, 2690-7.   DOI
10 Blum R, Jacob-Hirsch J, Amariglio N, et al (2005). Ras inhibition in glioblastoma down-regulates hypoxia-inducible factor- 1alpha, causing glycolysis shutdown and cell death. Cancer Res, 65, 999-1006.
11 Bos J L (1989). ras oncogenes in human cancer: a review. Cancer Res, 49, 4682-9.
12 Dallol A, Agathanggelou A, Fenton S L, et al (2004). RASSF1A interacts with microtubule-associated proteins and modulates microtubule dynamics. Cancer Res, 64, 4112-6.   DOI
13 Dallol A, Agathanggelou A, Tommasi S, et al (2005). Involvement of the RASSF1A tumor suppressor gene in controlling cell migration. Cancer Res, 65, 7653-9.
14 Dammann R, Li C, Yoon J H, et al (2000). Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3. Nat Genet, 25, 315-9.   DOI   ScienceOn
15 Jadon R, Pembroke C A, Hanna C L, et al (2014). A systematic review of organ motion and image-guided strategies in external beam radiotherapy for cervical cancer. Clin Oncol (R Coll Radiol), 26, 185-96.   DOI
16 Downward J (2003). Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer, 3, 11-22.   DOI   ScienceOn
17 Gao B N, Xie X J, Huang C X, et al (2008). RASSF1A polymorphism A133S is associated with early onset breast cancer in BRCA1/2 mutation carriers. Cancer Res, 68, 22-5.   DOI   ScienceOn
18 Goodsell D S (1999). The molecular perspective: the ras oncogene. Stem Cells, 17, 235-6.   DOI
19 Liu W J, Tan X H, Guo B P, et al (2013). Associations between RASSF1A promoter methylation and NSCLC: a metaanalysis of published data. Asian Pac J Cancer Prev, 14, 3719-24.   DOI   ScienceOn
20 Malumbres M , Barbacid M (2003). RAS oncogenes: the first 30 years. Nat Rev Cancer, 3, 459-65.   DOI
21 Parkin D M, Bray F, Ferlay J, et al (2005). Global cancer statistics, 2002. CA Cancer J Clin, 55, 74-108.   DOI   ScienceOn
22 Rahbari R, Sheahan T, Modes V, et al (2009). A novel L1 retrotransposon marker for HeLa cell line identification. Biotechniques, 46, 277-84.
23 Richter A M, Pfeifer G P , Dammann R H (2009). The RASSF proteins in cancer; from epigenetic silencing to functional characterization. Biochim Biophys Acta, 1796, 114-28.
24 Sherwood V, Recino A, Jeffries A, et al (2010). The N-terminal RASSF family: a new group of Ras-association-domaincontaining proteins, with emerging links to cancer formation. Biochem J, 425, 303-11.   DOI
25 Matallanas D, Romano D, Yee K, et al (2007). RASSF1A elicits apoptosis through an MST2 pathway directing proapoptotic transcription by the p73 tumor suppressor protein. Mol Cell, 27, 962-75.   DOI