Retinoic Acid Receptor-Beta as a Prognostic Indicator in Stage I Non–Small-Cell Lung Cancer

Khuri, Fadlo R.; Lotan, Reuben; Kemp, Bonnie L.; Lippman, Scott M.; Wu, Hong; Feng, Lei; Lee, John; Cooksley, Catherine S.; Parr, Bianca; Chang, E.L.; Walsh, Garrett L.; Lee, Jin S.; Hong, Waun Ki; Xu, Xiao Chun

doi:10.1200/jco.2000.18.15.2798

Cited by 94 publications

(62 citation statements)

References 26 publications

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“…COX-2, a marker of poor prognosis in stage I NSCLC, also is a promising target in treating NSCLC (34). Inhibition of COX-2 by selective COX-2 inhibitors enhances the response to chemotherapeutic regimens and leads to a prolonged progression-free survival when used in combination with radiotherapy (35,36).…”

Section: Discussionmentioning

confidence: 99%

Growth inhibition of non-small-cell lung carcinoma by BN/GRP antagonist is linked with suppression of K-Ras, COX-2, and pAkt

Hohla¹,

Schally²,

Kanashiro³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Section: Discussionmentioning

confidence: 99%

Growth inhibition of non-small-cell lung carcinoma by BN/GRP antagonist is linked with suppression of K-Ras, COX-2, and pAkt

Hohla¹,

Schally²,

Kanashiro³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…In situ hybridization A previously described method of nonradioactive in situ hybridization was used for detection of COX-2 expression (Khuri et al, 2001;Kong et al, 2005). The stained sections were reviewed in a manner similar to immunohistochemistry.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Induction of cyclooxygenase-2 by benzo[a]pyrene diol epoxide through inhibition of retinoic acid receptor-β2 expression

et al. 2005

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Benzo [a]pyrene diol epoxide (BPDE, a carcinogen present in tobacco smoke and environmental pollution) has been shown to suppress retinoic acid receptor-beta2 (RAR-b 2 ) and induce cyclooxygenase-2 (COX-2) expression. Restoration of RAR-b 2 inhibited growth and colony formation of esophageal cancer cells, which was correlated with COX-2 suppression. In this study, we investigated the molecular mechanisms for RAR-b 2 -mediated suppression of COX-2 expression using BPDE as a tool. We found that BPDE-induced COX-2 expression was through inhibition of RAR-b 2 and consequently, induction of epidermal growth factor receptor (EGFR), extracellular signal-regulated protein kinases 1/2 (Erk1/2) phosphorylation, and c-Jun expression. Esophageal cancer cells that do not express RAR-b 2 did not respond to BPDE for induction of COX-2. BPDE was also unable to induce COX-2 expression after RAR-b 2 expression was manipulated in these esophageal cancer cells. Furthermore, BPDE induced time-dependent methylation of RAR-b 2 gene promoter in esophageal cancer cells. Transfection of RAR-b 2 expression vector into esophageal cancer cells suppressed expression of EGFR, Erk1/2 phosphorylation, c-Jun, and COX-2. In addition, co-treatment of RAR-b 2 -positive cells with BPDE and the MEK1/2 inhibitor U0126 caused little change in c-Jun and COX-2 expression. This study demonstrated that BPDE-suppressed expression of RAR-b 2 results in COX-2 induction and restoration of RAR-b 2 expression reduces COX-2 protein in esophageal cancer cells, thereby further supporting our previous finding that RAR-b 2 plays an important role in suppressing esophageal carcinogenesis.

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“…2 Although RAR-β is effectively upregulated by 9cRA in bronchial epithelium, data implicating maintenance of RAR-β intratumorly in NSCLC patients showed a poorer prognosis have cast RAR-β in a less favorable light. 1,3 Retinoid refractoriness, in terms of inducing RAR-β expression or apoptosis with treatment of retinoids, is attributable, at least partially, to aberrant promoter methylation and histone H3 acetylation. One study showed retinoid receptor function to be intact in the t-RA-refractory malignant HBE cell line, however, suggesting that the defect in retinoid signaling in this lung carcinogenesis model was not intrinsic to the retinoid receptors.…”

Section: Introductionmentioning

confidence: 99%

9-cis retinoic acid induces insulin-like growth factor binding protein-3 through DR-8 Retinoic acid responsive elements

Chang

Cho²,

Cho³

et al. 2006

Cancer Biology & Therapy

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Retinoic Acid Receptor-Beta as a Prognostic Indicator in Stage I Non–Small-Cell Lung Cancer

Abstract: Unexpectedly, strong RAR-beta expression was associated with a significantly worse outcome of early-stage NSCLC. The mechanisms underlying this clinically and biologically important finding should be further explored.

Cited by 94 publications

References 26 publications

Growth inhibition of non-small-cell lung carcinoma by BN/GRP antagonist is linked with suppression of K-Ras, COX-2, and pAkt

Growth inhibition of non-small-cell lung carcinoma by BN/GRP antagonist is linked with suppression of K-Ras, COX-2, and pAkt

Induction of cyclooxygenase-2 by benzo[a]pyrene diol epoxide through inhibition of retinoic acid receptor-β2 expression

9-cis retinoic acid induces insulin-like growth factor binding protein-3 through DR-8 Retinoic acid responsive elements

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