Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

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)
  • Published : 2014.07.30
Download PDF
⟨ Previous Next ⟩

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

References

  1. 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.
  2. 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.
  3. 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. https://doi.org/10.1158/0008-5472.CAN-04-4088
  4. 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. https://doi.org/10.1158/0008-5472.CAN-04-3593
  5. 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. https://doi.org/10.1016/j.molcel.2005.05.010
  6. 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.
  7. Bos J L (1989). ras oncogenes in human cancer: a review. Cancer Res, 49, 4682-9.
  8. 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. https://doi.org/10.1158/0008-5472.CAN-04-0267
  9. 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.
  10. 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. https://doi.org/10.1038/77083
  11. Downward J (2003). Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer, 3, 11-22. https://doi.org/10.1038/nrc969
  12. 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. https://doi.org/10.1158/0008-5472.CAN-07-5183
  13. Goodsell D S (1999). The molecular perspective: the ras oncogene. Stem Cells, 17, 235-6. https://doi.org/10.1002/stem.170235
  14. 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. https://doi.org/10.1016/j.clon.2013.11.031
  15. 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. https://doi.org/10.7314/APJCP.2013.14.6.3719
  16. Malumbres M , Barbacid M (2003). RAS oncogenes: the first 30 years. Nat Rev Cancer, 3, 459-65. https://doi.org/10.1038/nrc1097
  17. 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. https://doi.org/10.1016/j.molcel.2007.08.008
  18. Parkin D M, Bray F, Ferlay J, et al (2005). Global cancer statistics, 2002. CA Cancer J Clin, 55, 74-108. https://doi.org/10.3322/canjclin.55.2.74
  19. Rahbari R, Sheahan T, Modes V, et al (2009). A novel L1 retrotransposon marker for HeLa cell line identification. Biotechniques, 46, 277-84.
  20. 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.
  21. 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. https://doi.org/10.1042/BJ20091318
  22. 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. https://doi.org/10.7314/APJCP.2013.14.1.81
  23. 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. https://doi.org/10.1128/MCB.25.18.8356-8367.2005
  24. 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. https://doi.org/10.1074/jbc.M512128200
  25. 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. https://doi.org/10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F

Cited by

  1. Aberrant Methylation of RASSF1A gene Contribute to the Risk of Renal Cell Carcinoma: a Meta-Analysis vol.16, pp.11, 2015, https://doi.org/10.7314/APJCP.2015.16.11.4665
  2. Association between RASSF1A Promoter Hypermethylation and Oncogenic HPV Infection Status in Invasive Cervical Cancer: a Meta-analysis vol.16, pp.14, 2015, https://doi.org/10.7314/APJCP.2015.16.14.5749
  3. The tumor suppressive role of RASSF1A in osteosarcoma through the Wnt signaling pathway vol.37, pp.7, 2016, https://doi.org/10.1007/s13277-015-4660-z