© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 15, 1317-1321,
August 4, 1999
© 1999 Oxford University Press
REPORTS |
Nuclear Retinoid Acid Receptor Beta in Bronchial Epithelium of Smokers Before and During Chemoprevention
Affiliations of authors: X.-C. Xu, X. Liu, S. M. Lippman (Department of Clinical Cancer Prevention), J. S. Lee, R. C. Morice, W. K. Hong, R. Lotan (Department of Thoracic/Head and Neck Medical Oncology), J. J. Lee (Department of Biomathematics), The University of Texas M. D. Anderson Cancer Center, Houston.
Correspondence to: Reuben Lotan, Ph.D., Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030 (e-mail: rlotan{at}notes.mdacc.tmc.edu).
BACKGROUND: Retinoids can reverse neoplastic lesions and prevent second primary tumors in
the aerodigestive tract. These effects are thought to be mediated by nuclear retinoic acid receptors
(RARs) and retinoid X receptors (RXRs), each receptor group including three subtypes (
,
ß, and 
). Previously, we found that RARß expression was suppressed in lung
cancer. In this study, we investigated whether expression of RARß is modulated by
chemopreventive intervention. METHODS: Using in situ hybridization, we analyzed
RARß messenger RNA (mRNA) expression in bronchial biopsy specimens from heavy
smokers, at baseline and after 6 months of treatment with 13-cis-retinoic acid (13-cis-RA) or placebo. Since we had previously detected RARß expression in 90%
of
bronchial specimens from nonsmokers, we considered loss of RARß mRNA expression in at
least one of six biopsy specimens at baseline in this study to be aberrant. RESULTS: RARß
mRNA expression was aberrant in 30 (85.7%) of 35 subjects in the 13-cis-RA
group and in 24 (72.7%) of 33 subjects in the placebo group. After 6 months of 13-cis-RA treatment, the number of subjects who were RARß positive in all six biopsy
specimens increased from five of 35 to 13 of 35 (2.6-fold), so that the percentage of individuals
with aberrant RARß expression decreased to 62.9% (22 of 35), which represents a
statistically significant difference from baseline expression (two-sided P = .01).
In
the placebo group, no statistically significant difference in RARß expression was observed
between baseline and 6 months. RARß expression was not related to current smoking status
or reversal of squamous metaplasia. CONCLUSIONS: These results indicate that RARß is
an independent marker of response to 13-cis-RA and may serve as an intermediate
biomarker in chemoprevention trials of upper aerodigestive tract cancers.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Kadara, L. Lacroix, C. Behrens, L. Solis, X. Gu, J. J. Lee, E. Tahara, D. Lotan, W. K. Hong, I. I. Wistuba, et al. Identification of Gene Signatures and Molecular Markers for Human Lung Cancer Prognosis using an In vitro Lung Carcinogenesis System Cancer Prevention Research, August 1, 2009; 2(8): 702 - 711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kelly, J. Kittelson, W. A. Franklin, T. C. Kennedy, C. E. Klein, R. L. Keith, E. C. Dempsey, M. Lewis, M. K. Jackson, F. R. Hirsch, et al. A Randomized Phase II Chemoprevention Trial of 13-CIS Retinoic Acid with Or without {alpha} Tocopherol or Observation in Subjects at High Risk for Lung Cancer Cancer Prevention Research, May 1, 2009; 2(5): 440 - 449. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Sedjo, J. Ranger-Moore, J. Foote, N. E. Craft, D. S. Alberts, M.-J. Xu, and A. R. Giuliano Circulating Endogenous Retinoic Acid Concentrations among Participants Enrolled in a Randomized Placebo-Controlled Clinical Trial of Retinyl Palmitate Cancer Epidemiol. Biomarkers Prev., November 1, 2004; 13(11): 1687 - 1692. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. R. Khuri and R. Lotan Retinoids in Lung Cancer: Friend, Foe, or Fellow Traveler? J. Clin. Oncol., September 1, 2004; 22(17): 3435 - 3437. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Prakash, C. Liu, K.-Q. Hu, N. I. Krinsky, R. M. Russell, and X.-D. Wang {beta}-Carotene and {beta}-Apo-14'-Carotenoic Acid Prevent the Reduction of Retinoic Acid Receptor {beta} in Benzo[a]pyrene-Treated Normal Human Bronchial Epithelial Cells J. Nutr., March 1, 2004; 134(3): 667 - 673. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Vourlekis and E. Szabo Predicting Success in Cancer Prevention Trials J Natl Cancer Inst, February 5, 2003; 95(3): 178 - 179. [Full Text] [PDF]
|
|
|
|
|
|
J. M. Kurie, R. Lotan, J. J. Lee, J. S. Lee, R. C. Morice, D. D. Liu, X.-C. Xu, F. R. Khuri, J. Y. Ro, W. N. Hittelman, et al. Treatment of Former Smokers With 9-cis-Retinoic Acid Reverses Loss of Retinoic Acid Receptor-{beta} Expression in the Bronchial Epithelium: Results From a Randomized Placebo-Controlled Trial J Natl Cancer Inst, February 5, 2003; 95(3): 206 - 214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-C. Soria, X. Xu, D. D. Liu, J. J. Lee, J. Kurie, R. C. Morice, F. Khuri, L. Mao, W. K. Hong, and R. Lotan Retinoic Acid Receptor {beta} and Telomerase Catalytic Subunit Expression in Bronchial Epithelium of Heavy Smokers J Natl Cancer Inst, January 15, 2003; 95(2): 165 - 168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Zochbauer-Muller, J. D. Minna, and A. F. Gazdar Aberrant DNA Methylation in Lung Cancer: Biological and Clinical Implications Oncologist, October 1, 2002; 7(5): 451 - 457. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Lippman and M. R. Spitz Lung Cancer Chemoprevention: An Integrated Approach J. Clin. Oncol., September 15, 2001; 19(90001): 74s - 82. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Pastorino Molecular Targeting: the New Challenge in Lung Cancer Prevention J Natl Cancer Inst, August 15, 2001; 93(16): 1190 - 1191. [Full Text] [PDF]
|
|
|
|
|
|
J.-C. Soria, C. Moon, L. Wang, W. N. Hittelman, S. J. Jang, S.-Y. Sun, J. J. Lee, D. Liu, J. M. Kurie, R. C. Morice, et al. Effects of N-(4-Hydroxyphenyl)retinamide on hTERT Expression in the Bronchial Epithelium of Cigarette Smokers J Natl Cancer Inst, August 15, 2001; 93(16): 1257 - 1263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. I. Song, M. N. Lango, J. D. Hwang, S. D. Drenning, Q. Zeng, W. W. Lamph, and J. R. Grandis Abrogation of Transforming Growth Factor-{alpha}/Epidermal Growth Factor Receptor Autocrine Signaling by an RXR-selective Retinoid (LGD1069, Targretin) in Head and Neck Cancer Cell Lines Cancer Res., August 1, 2001; 61(15): 5919 - 5925. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Lippman, J. J. Lee, D. D. Karp, E. E. Vokes, S. E. Benner, G. E. Goodman, F. R. Khuri, R. Marks, R. J. Winn, W. Fry, et al. Randomized Phase III Intergroup Trial of Isotretinoin to Prevent Second Primary Tumors in Stage I Non-Small-Cell Lung Cancer J Natl Cancer Inst, April 18, 2001; 93(8): 605 - 618. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. R. Khuri, H. Wu, J. J. Lee, B. L. Kemp, R. Lotan, S. M. Lippman, L. Feng, W. K. Hong, and X.-C. Xu Cyclooxygenase-2 Overexpression Is a Marker of Poor Prognosis in Stage I Non-Small Cell Lung Cancer Clin. Cancer Res., April 1, 2001; 7(4): 861 - 867. [Abstract] [Full Text]
|
|
|
|
|
|
A. F. Gazdar, S. Zochbauer-Moller, A. Virmani, J. Kurie, J. D. Minna, and S. Lam RESPONSE: Re: Promoter Methylation and Silencing of the Retinoic Acid Receptor-{{beta}} Gene in Lung Carcinomas J Natl Cancer Inst, January 3, 2001; 93(1): 67 - 68. [Full Text] [PDF]
|
|
|
|
|
|
W. K. Hong, M. R. Spitz, and S. M. Lippman Cancer Chemoprevention in the 21st Century: Genetics, Risk Modeling, and Molecular Targets J. Clin. Oncol., November 1, 2000; 18(90001): 9s - 18. [Full Text] [PDF]
|
|
|
|
|
|
F. R. Khuri, R. Lotan, B. L. Kemp, S. M. Lippman, H. Wu, L. Feng, J. J. Lee, C. S. Cooksley, B. Parr, E. Chang, et al. Retinoic Acid Receptor-Beta as a Prognostic Indicator in Stage I Non-Small-Cell Lung Cancer J. Clin. Oncol., August 15, 2000; 18(15): 2798 - 2804. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Kurie, J. S. Lee, F. R. Khuri, L. Mao, R. C. Morice, J. J. Lee, G. L. Walsh, A. Broxson, S. M. Lippman, J. Y. Ro, et al. N-(4-Hydroxyphenyl)Retinamide in the Chemoprevention of Squamous Metaplasia and Dysplasia of the Bronchial Epithelium Clin. Cancer Res., August 1, 2000; 6(8): 2973 - 2979. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. TOULOUSE, M. LOUBEAU, J. MORIN, J. J. PAPPAS, J. WU, and W. E. C. BRADLEY RAR{beta} involvement in enhancement of lung tumor cell immunogenicity revealed by array analysis FASEB J, June 1, 2000; 14(9): 1224 - 1232. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Zhang, A. K. Rishi, M. I. Dawson, R. Tschang, L. Farhana, M. Boyanapalli, U. Reichert, B. Shroot, E. C. Van Buren, and J. A. Fontana S-phase Arrest and Apoptosis Induced in Normal Mammary Epithelial Cells by a Novel Retinoid Cancer Res., April 1, 2000; 60(7): 2025 - 2032. [Abstract] [Full Text]
|
|
|
|
|
|
M. J. Spinella and E. Dmitrovsky Aberrant Retinoid Signaling and Breast Cancer: the View From Outside the Nucleus J Natl Cancer Inst, March 15, 2000; 92(6): 438 - 440. [Full Text] [PDF]
|
|
|
|
|
|
S. M. Lippman and R. Lotan Advances in the Development of Retinoids as Chemopreventive Agents J. Nutr., February 1, 2000; 130(2): 479 - 479. [Abstract] [Full Text]
|
|
|
|
|
|
S. M. Lippman and P. H. Brown Tamoxifen Prevention of Breast Cancer: an Instance of the Fingerpost J Natl Cancer Inst, November 3, 1999; 91(21): 1809 - 1819. [Full Text] [PDF]
|
|
|
|
|
|
J. Ayoub, R. Jean-Francois, Y. Cormier, D. Meyer, Y. Ying, P. Major, C. Desjardins, and W.E.C. Bradley Placebo-Controlled Trial of 13-cis-Retinoic Acid Activity on Retinoic Acid Receptor-Beta Expression in a Population at High Risk: Implications for Chemoprevention of Lung Cancer J. Clin. Oncol., November 1, 1999; 17(11): 3546 - 3552. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-Y. Sun, H. Wan, P. Yue, W. K. Hong, and R. Lotan Evidence That Retinoic Acid Receptor beta Induction by Retinoids Is Important for Tumor Cell Growth Inhibition J. Biol. Chem., May 26, 2000; 275(22): 17149 - 17153. [Abstract] [Full Text] [PDF]
|
|