HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by TOULOUSE, A. Articles by BRADLEY, W. E. C. Search for Related Content PubMed PubMed Citation Articles by TOULOUSE, A. Articles by BRADLEY, W. E. C.

RARß involvement in enhancement of lung tumor cell immunogenicity revealed by array analysis

ANDRÉ TOULOUSE^*,1, MARTINE LOUBEAU, JOHANE MORIN^*,, JANE J. PAPPAS^*,, JIANGPING WU^,,§ and W. EDWARD C. BRADLEY^*,,,¶

^* Institut du Cancer de Montreal,
Centre de Recherche du CHUM 1560 Sherbrooke E., Montréal, Qc, H2L 4M1, Canada;
Départment de Médecine, Université de Montréal, and Departments of
^§ Surgery and
^¶ Oncology, McGill University, Montréal, Qc, H3G 1Y6, Canada

¹Correspondence: Montreal General Hospital Research Institute, Rm. L12–132, 1650 Cedar Ave., Montréal, Canada H3G 1A4. E-mail: mbem{at}musica.mcgill.ca

The retinoid receptors (RARs and RXRs) are mediators of the multiple effects of retinoic acid. Of these, the retinoic acid receptor ß2 (RARß2) has frequently been shown to be the principal mediator of the growth and tumor suppressive effects of retinoic acid; this gene is inactivated in many epithelial tumors and their derived cell lines. We have searched for genes that are regulated by this isoform and are potentially involved in tumor suppression. Using the Atlas human cDNA array I, we identified 27 genes (not counting RARß itself) that are regulated, directly or indirectly, by RARß2 when it is transfected into Calu-1, a lung tumor-derived line that does not normally express RARß. Several of the affected genes code for proteins whose functions would augment the process of apoptosis and/or the host’s immune response. The latter group included ICAM-1 and MHC class I heavy chain, whose protein products play particularly important roles in the mounting of an effective anti-tumor response. We then confirmed by flow cytometry that the observed increases in message levels were reflected in increased cell surface protein levels for ICAM-1 and MHC class I in RARß2 transfectants of two RARß-deficient lines, Calu-1 and the epidermoid lung cancer-derived line SK-MES. Finally, we showed that RARß2 transfection of Calu-1 cells enhanced the heterologous CTL response in both the induction and the effector phases by up to threefold. These results support the hypothesis that down-regulation of these genes (and possibly others) in RARß-deficient tumor cells contributes to immune system evasion, and suggest a novel therapeutic approach for this disease.—Toulouse, A., Loubeau, M., Morin, Pappas, J. J., Wu, J., Bradley W. E. C. RARß involvement in enhancement of lung tumor cell immunogenicity revealed by array analysis.

Key Words: lung cancer • retinoic acid receptor ß • tumor suppression • cDNA array

This article has been cited by other articles:

				Z. D. Liang, S. M. Lippman, T.-T. Wu, R. Lotan, and X.-C. Xu RRIG1 Mediates Effects of Retinoic Acid Receptor {beta}2 on Tumor Cell Growth and Gene Expression through Binding to and Inhibition of RhoA. Cancer Res., July 15, 2006; 66(14): 7111 - 7118. [Abstract] [Full Text] [PDF]

				D. P. Simmons, M. L. Peach, J. R. Friedman, M. M.B. Green, M. C. Nicklaus, and L. M. De Luca Evidence that sequence homologous region in LRAT-like proteins possesses anti-proliferative activity and DNA binding properties: translational implications and mechanism of action Carcinogenesis, April 1, 2006; 27(4): 693 - 707. [Abstract] [Full Text] [PDF]

				S. Mocellin, E. Wang, M. Panelli, P. Pilati, and F. M. Marincola DNA Array-Based Gene Profiling in Tumor Immunology Clin. Cancer Res., July 15, 2004; 10(14): 4597 - 4606. [Abstract] [Full Text] [PDF]

				Y. Zhuang, T. N. Faria, P. Chambon, and L. J. Gudas Identification and Characterization of Retinoic Acid Receptor {beta}2 Target Genes in F9 Teratocarcinoma Cells Mol. Cancer Res., June 1, 2003; 1(8): 619 - 630. [Abstract] [Full Text] [PDF]

				S. M. Sirchia, M. Ren, R. Pili, E. Sironi, G. Somenzi, R. Ghidoni, S. Toma, G. Nicolo, and N. Sacchi Endogenous Reactivation of the RAR{beta}2 Tumor Suppressor Gene Epigenetically Silenced in Breast Cancer Cancer Res., May 1, 2002; 62(9): 2455 - 2461. [Abstract] [Full Text] [PDF]

				R. K. Blanchard, J. B. Moore, C. L. Green, and R. J. Cousins Inaugural Article: Modulation of intestinal gene expression by dietary zinc status: Effectiveness of cDNA arrays for expression profiling of a single nutrient deficiency PNAS, November 20, 2001; 98(24): 13507 - 13513. [Abstract] [Full Text] [PDF]