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Identification of RASSF1A modulated genes in nasopharyngeal carcinoma

Oncogene volume 25, pages 310–316 (2006)Cite this article

Abstract

RASSF1A is a tumor suppressor gene on 3p21.3 frequently inactivated by promoter hypermethylation in nasopharyngeal carcinoma (NPC). To identify RASSF1A target genes in NPC, we have investigated the expression profile of the stable RASSF1A transfectants and controls by high-density oligonucleotide array. A total of 57 genes showed differential expression in the RASSF1A-expressing cells. These RASSF1A target genes were involved in multiple cellular regulatory processes such as transcription, signal transduction, cell adhesion and RNA processing. The RASSF1A-modulated expression of eight selected genes with the highest fold changes (ATF5, TCRB, RGS1, activin βE, HNRPH1, HNRPD, Id2 and CKS2) by RASSF1A was confirmed in both stable and transient transfectants. Compared with the RASSF1A transfectants, an inverse expression pattern of activin βE, Id2 and ATF5 was shown in the immortalized nasopharyngeal epithelial cells treated with siRNA against RASSF1A. The findings imply that the expression of activin βE, Id2 and ATF5 was tightly regulated by RASSF1A and may associate with its tumor suppressor function. Strikingly, overexpression of Id2 is common in NPC and RASSF1A-induced repression of Id2 was mediated by the overexpression of activin βE. The results suggest a novel RASSF1A pathway in which both activin βE and Id2 are involved.

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Accession codes

Accessions

GenBank/EMBL/DDBJ

Abbreviations

NPC:

nasopharyngeal carcinoma

Id2 :

inhibitor of differeniation 2

LOH:

loss of heterozygosity

siRNA:

small-interfering RNA

TGFβ:

transforming growth factor beta

BMP:

bone morphogenetic protein

QRT–PCR:

quantitative reverse-transcription polymerase chain reaction

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Acknowledgements

This work was carried out under the supervision and supports of Professor Dolly P Huang who recently deceased. Her input significantly contributed to this study. This manuscript is dedicated to Professor Huang in memory of her invaluable guidance. Mouse anti-human RGS1 antibody was a generous gift from Dr Xiao-Hui Li, the Center for Biomedical Inventions, University of Texas Southwestern at Dallas. This work is supported by the Kadoorie Charitable Foundations and Hong Kong Research Grant Council (CUHK 4255/04M; CUHK 4410/03M; HKUST 2/03C).

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Author notes

  1. L S-N Chow and C-W Lam: These authors contributed equally to this work

  2. D P Huang: Professor DP Huang is deceased

Authors and Affiliations

  1. Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR

    L S-N Chow, S Y-Y Chan, K-F To, W-K Hung, D P Huang & K-W Lo

  2. Department of Chemical Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR

    C-W Lam & S-F Tong

  3. Department of Anatomy, University of Hong Kong, Hong Kong SAR

    S-W Tsao

  4. Institut für Humangenetik und Medizinische Biologie, Martin-Luther-Universität Halle-Wittenberg, Halle/Saale, D-06097, Germany

    R Dammann

Authors
  1. L S-N Chow
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  2. C-W Lam
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Correspondence to K-W Lo.

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Chow, LN., Lam, CW., Chan, SY. et al. Identification of RASSF1A modulated genes in nasopharyngeal carcinoma. Oncogene 25, 310–316 (2006). https://doi.org/10.1038/sj.onc.1209001

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