Epigenetic inactivation of the RAS-effector gene RASSF2 in lung cancers

  • Authors:
    • Kyoichi Kaira
    • Noriaki Sunaga
    • Yoshio Tomizawa
    • Noriko Yanagitani
    • Tamotsu Ishizuka
    • Ryusei Saito
    • Takashi Nakajima
    • Masatomo Mori
  • View Affiliations

  • Published online on: July 1, 2007     https://doi.org/10.3892/ijo.31.1.169
  • Pages: 169-173
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Abstract

RASSF2, a member of the RAS association domain family 1 (RASSF1), is a candidate tumor suppressor gene (TSG) that is silenced by promoter hypermethylation in several human cancers. In this study, we examined the expression of RASSF2 mRNA and the promoter methylation status in lung cancer cell lines and in tumor samples of 106 primary non-small cell lung cancers (NSCLCs) by methylation-specific PCR. RASSF2 expression was absent in 26% of small cell lung cancers (SCLCs; n=27 lines) and 50% of NSCLCs (n=42 lines). Promoter methylation of RASSF2 was found in 18% of the SCLC cell lines (n=22) and 62% of the NSCLC cell lines (n=26), and the methylation status was tightly associated with the loss of RASSF2 expression. RASSF2 expression was restored by treatment with 5-aza-2-deoxycytidine and/or trichostatin-A in the NSCLC cell lines which were absent of the expression. RASSF2 methylation was found in 31% of primary NSCLC tumors, and methylation was more frequent in the specimens from non-smokers (18 of 40, 45%) than in the specimens from smokers (15 of 66, 23%, P=0.014). We also examined the association of RASSF2 methylation with mutations of KRAS and EGFR and with promoter hypermethylation of RASSF1A; however, we could not find a significant association between RASSF2 methylation and these genetic and epigenetic changes. Our results indicate that aberrant methylation of the RASSF2 gene with the subsequent loss of RASSF2 expression plays an important role in the pathogenesis of lung cancers.

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July 2007
Volume 31 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Kaira K, Sunaga N, Tomizawa Y, Yanagitani N, Ishizuka T, Saito R, Nakajima T and Mori M: Epigenetic inactivation of the RAS-effector gene RASSF2 in lung cancers. Int J Oncol 31: 169-173, 2007.
APA
Kaira, K., Sunaga, N., Tomizawa, Y., Yanagitani, N., Ishizuka, T., Saito, R. ... Mori, M. (2007). Epigenetic inactivation of the RAS-effector gene RASSF2 in lung cancers. International Journal of Oncology, 31, 169-173. https://doi.org/10.3892/ijo.31.1.169
MLA
Kaira, K., Sunaga, N., Tomizawa, Y., Yanagitani, N., Ishizuka, T., Saito, R., Nakajima, T., Mori, M."Epigenetic inactivation of the RAS-effector gene RASSF2 in lung cancers". International Journal of Oncology 31.1 (2007): 169-173.
Chicago
Kaira, K., Sunaga, N., Tomizawa, Y., Yanagitani, N., Ishizuka, T., Saito, R., Nakajima, T., Mori, M."Epigenetic inactivation of the RAS-effector gene RASSF2 in lung cancers". International Journal of Oncology 31, no. 1 (2007): 169-173. https://doi.org/10.3892/ijo.31.1.169