© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 12, 1059-1066,
June 16, 1999
© 1999 Oxford University Press
REPORTS |
Expression of Retinoid Receptor Genes and Proteins in Non-Small-Cell Lung Cancer
Affiliations of authors: E. Picard (Laboratoire d'Anatomie Pathologique), C. Seguin, N. Martinet (Institut National de la Santé et de la Recherche Médicale [INSERM] U14), N. Monhoven (Laboratoire Commun de Biologie Moléculaire), J. Siat, J. Borrelly (Clinique Pneumologique Médico-Chirurgicale), Centre Hospitalier Universitaire de Nancy, France; C. Rochette-Egly, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/INSERM/Université Louis Pasteur, Communauté Urbaine de Strasbourg, France; Y. Martinet, INSERM U14 and Clinique Pneumologique Médico-Chirurgicale; J. M. Vignaud, Laboratoire d'Anatomie Pathologique and INSERM U14.
Correspondence to: Jean Michel Vignaud, M.D., Laboratoire d'Anatomie Pathologique, Hopital Central, 54035 Nancy cedex, France (e-mail: jm.vignaud{at}chu-nancy.fr).
BACKGROUND: Retinoids can suppress carcinogenesis in high-risk non-neoplastic bronchial
lesions and can reduce the risk of second primary non-small-cell lung cancer (NSCLC). The
effects of retinoids are mediated by nuclear receptors, i.e., the retinoic acid receptors (RAR
,
RARß, and RAR
) and the retinoid X receptors (RXR, RXRß, and
RXR). We investigated whether abnormalities in the in vivo expression of
retinoid receptors are observed in NSCLC. METHODS: Expression of retinoid receptors in
paired specimens of normal and cancerous tissues from the lungs of 76 patients with NSCLC was
studied by use of anti-retinoid receptor antibodies (except those against RXR) and
immunohistochemistry. RAR messenger RNAs were analyzed by use of in situ hybridization and by reverse transcription-polymerase chain reaction (RT-PCR). Samples were
also studied for loss of heterozygosity (LOH) at chromosome 3p24. All P values are
two-sided. RESULTS: All studied receptors were expressed in normal lung cells and in high-
risk non-neoplastic lesions. In tumor cells, overexpression of RXR and RAR was
frequently observed. In contrast, RXRß expression decreased in 18% of the tumor
specimens. Furthermore, there was a marked decrease in the expression of RARß in
63% of the tumors (P<.0001). Decreased expression of RAR was
observed by RT-PCR in 41% of the tumors (P<.0001). LOH at 3p24 was
observed in 41% of the tumor specimens from informative patients and in 20% of
the non-neoplastic lesions. CONCLUSIONS: Expression of RAR and RXR is either
normal or elevated in NSCLC. In contrast, a large percentage of tumors show a marked decrease
in the expression of RARß, RAR, and RXRß as well as a high frequency of LOH
at 3p24, which was also observed in non-neoplastic lesions. These data suggest that altered
retinoid receptor expression may play a role in lung carcinogenesis.
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