1. ¹Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR
2. ²Department of Chemical Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR
3. ³Department of Anatomy, University of Hong Kong, Hong Kong SAR
4. ⁴Institut für Humangenetik und Medizinische Biologie, Martin-Luther-Universität Halle-Wittenberg, D-06097 Halle/Saale, Germany

Correspondence: Dr K-W Lo, E-mail: kwlo@cuhk.edu.hk

⁵These authors contributed equally to this work

Professor DP Huang is deceased

Received 23 March 2005; Revised 8 July 2005; Accepted 8 July 2005; Published online 22 August 2005.

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 E, 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 E, Id2 and ATF5 was shown in the immortalized nasopharyngeal epithelial cells treated with siRNA against RASSF1A. The findings imply that the expression of activin E, 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 E. The results suggest a novel RASSF1A pathway in which both activin E and Id2 are involved.