Retinoic Acid Receptor-β Expression in Stage I Non-Small Cell Lung Cancer and Adjacent Normal Appearing Bronchial Epithelium
Yoon Soo ChangJae Ho ChungDong Hwan ShinKyung Soo ChungYoung Sam KimJoon ChangSung Kyu KimSoon Il Kim
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Retinoic acid receptor-beta (RAR-beta) is induced by and mediates the growth-inhibitory and apoptotic effects of retinoic acid (RA), suggesting that loss of RAR-beta expression may be one of the critical events involved in the carcinogenesis/ progression of non-small cell lung cancer (NSCLC) and in the responsiveness to retinoid chemotherapy. However, recent contradictory reports that the expression of RAR-beta is associated with poor clinical outcome, and the fact that treatment of serum-deprived type 2 alveolar cells with RA leads to a stimulation of cell proliferation, require the verification of RAR-beta as a biomarker of chemoprevention or prognosis. The expression status of RAR-beta in cancer cells and adjacent normal appearing bronchial epithelium from 39 patients, diagnosed as stage I NSCLC and undergone a curative lung resection, was analyzed in paraffin-embedded tissue sections by IHC staining. The normal appearing bronchial epithelium of 14 out of 33 (42.4%) specimens expressed RAR-beta, whereas 22 out of the 39 (56.4%) stage I NSCLC specimens expressed RAR-beta. RAR-beta was more frequently expressed in the adenocarcinoma (72.7%) than in the squamous cell carcinoma (31.3%) (p=0.026). Neither the expression status in normal appearing adjacent tissue nor that in the tumor tissue had prognostic implications. The higher expression of RAR-beta in cancer tissue, the focal and uneven distribution in normal appearing adjacent bronchial epithelium, and inconsistency with the corresponding tumor tissue, suggest that the expression status of RAR-beta as a biomarker for chemoprevention/early diagnosis or the prognosis of NSCLC requires further consideration.Journal Article Expression of a Retinoic Acid–Receptor Gene Is Regulated by Retinoic Acid Itself Get access Nutrition Reviews, Volume 48, Issue 9, September 1990, Pages 355–357, https://doi.org/10.1111/j.1753-4887.1990.tb02982.x Published: 01 September 1990
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Tretinoin
Retinoid X receptor
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The objective of this study was to compare the properties of 9-cis and all-trans retinoic acid with respect to the induction of expression of retinoic acid receptor beta (RAR-beta) and cellular retinoic acid-binding protein (CRABP) II in human neuroblastoma SH SY 5Y cells. RAR-beta and CRABP II mRNA was induced by both all-trans and 9-cis retinoic acid in SH SY 5Y cells. Induction was rapid, detectable within 2-4 h, and inhibited by actinomycin D. Time-courses of induction for RAR-beta and CRABP II differed: RAR-beta mRNA levels reached a maximum 4-6 h after adding all-trans or 9-cis retinoic acid, whereas CRABP II mRNA levels increased over at least 18 h. These differences were attributed to the longer half-life of CRABP II mRNA (20 h) compared with RAR-beta mRNA (3.9 h). The dose-response characteristics of all-trans and 9-cis retinoic acid were different: all-trans was effective at nanomolar concentrations, whereas 10-fold higher levels of 9-cis retinoic acid were required to achieve comparable induction of RAR-beta and CRABP II. Conversely, at high concentrations, 9-cis retinoic acid gave a greater induction of RAR-beta and CRABP II than all-trans. The induction of RAR-beta and CRABP II by all-trans retinoic acid was maintained in the subsequent absence of all-trans retinoic acid, whereas induction by 9-cis retinoic acid was dependent on its continued presence in the culture medium. These results suggest that, at high concentrations, 9-cis retinoic acid may produce its transcriptional effects via retinoid X receptor (RXR) homodimers. This has implications for the cellular functions of 9-cis retinoic acid and its use as a biological response modifier.
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Tissue transglutaminase
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Cellular retinoic acid-binding protein II (CRABP-II) is an intracellular lipid-binding protein that associates with retinoic acid with a subnanomolar affinity.We previously showed that CRABP-II enhances the transcriptional activity of the nuclear receptor with which it shares a common ligand, namely, the retinoic acid receptor (RAR), and we suggested that it may act by delivering retinoic acid to this receptor.Here, the mechanisms underlying the effects of CRABP-II on the transcriptional activity of RAR and the functional consequences of these effects were studied.We show that CRABP-II, a predominantly cytosolic protein, massively undergoes nuclear localization upon binding of retinoic acid; that it interacts with RAR in a ligand-dependent fashion; and that, in the presence of retinoic acid, the CRABP-II-RAR complex is a short-lived intermediate.The data establish that potentiation of the transcriptional activity of RAR stems directly from the ability of CRABP-II to channel retinoic acid to the receptor.We demonstrate further that overexpression of CRABP-II in MCF-7 mammary carcinoma cells dramatically enhances their sensitivity to retinoic acid-induced growth inhibition.Conversely, diminished expression of CRABP-II renders these cells retinoic acid resistant.Taken together, the data unequivocally establish the function of CRABP-II in modulating the RAR-mediated biological activities of retinoic acid.
Tretinoin
Retinoid X receptor
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Objective:To explore whether there are abnormalities in the expression of retinoic acid receptors in breast cancer tissues. Methods:Expression of retinoic acid receptors was detected in 49 breast cancer patients by using reverse transcription-polymerase chain reaction. Results:Retinoic acid receptor 001). The loss of retinoic acid receptor
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