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At least 991 records · Page 55Linked to original sources
PubMed1999

Retinoic acid receptors and retinoid X receptors in the rat testis during fetal and postnatal development: immunolocalization and implication in the control of the number of gonocytes.

Retinoids have pleiotropic effects on embryonic development and are essential for spermatogenesis in the adult, where they act via nuclear retinoid receptors: retinoic acid receptors (RARs) and retinoid X receptors (RXRs). We used immunohistochemistry to examine the cellular localization of RARs and RXRs in the rat testis from Day 13.5 postconception (13.5 dpc) until Day 8 postpartum (8 dpp), and these findings were compared with those for immature and adult testes. RARalpha and RARbeta were detected in the interstitial tissue from 14.5 dpc, with intense staining in the gonocytes from 20. 5 dpc to 8 dpp. The nuclei of all cell types stained faintly for RARgamma from 8 dpp. Immunoreactivity for RXRalpha was intense in the gonocytes from 13.5 dpc and in the Leydig cells from 16.5 dpc, and persisted throughout the period studied. RXRbeta was always detected in the Leydig cells and during a short neonatal period in the gonocytes. RXRgamma gave a faint reaction in the nuclei of all cell types from 20.5 dpc. Unexpectedly, immunostaining for all the receptors tested, except RARgamma and RXRgamma, was detected in the cytoplasmic compartment of the cells of fetal and neonatal testes, while it was found in the nuclei in immature and adult testes. In cultures of dispersed testicular cells from 3 dpp pups, retinoic acid had a dose-dependent deleterious effect on the survival of the gonocytes and, to a lesser extent, of the somatic cells. These results suggest that retinoids act on the testicular development, especially on germ cells, via RARs and/or RXRs.

Animals↗
PubMed2002

Linkage between retinoid and fatty acid receptors: implications for breast cancer prevention.

Certain dietary retinoids and polyunsaturated fatty acids (PUFAs) consistently inhibit progression of mammary carcinogenesis both in animal studies and cell culture, but clinically, their effect is inconsistent. New evidence of synergistic interaction between the nuclear receptors for the two groups of nutritional agents suggests that appropriate selective ligands from each group might be combined in breast cancer chemoprevention studies. Peroxisome proliferator-activated receptor (PPAR) gamma is a nuclear receptor that is activated by PUFAs, eicosanoids and antidiabetic agents such as troglitazone. Such activation can cause growth inhibition in human mammary cancer cells in culture and the effect is enhanced by ligands of retinoic acid receptor (RAR) and retinoid X receptor (RXR). In mouse mammary tissue in organ culture, an RXR-selective ligand has been shown to enhance the effect of troglitazone in suppressing carcinogen-induced pre-neoplastic changes. A PPAR/RXR heterodimer is involved in tumour growth inhibition and has been shown to bind directly to nuclear oestrogen response elements (ERE) independently of oestrogen receptor (ER) activity. A combination of an RXR-selective retinoid with either troglitazone or else a long-chain n-3 PUFA, is proposed for a short-term study in postmenopausal women after primary surgery for intraductal breast cancer. The resulting activation of PPAR/RXR expression may increase response to retinoid administration, especially in the presence of obesity and insulin resistance, because of the ability of PPAR gamma ligands to reduce insulin-like growth factor I (IGF-I) concentrations. Serial core biopsies of breast tissue over a short term are proposed to identify changes in phenotype, which may influence progression to invasiveness. In addition to cytomorphological criteria, expression of ER alpha and beta, RAR alpha and beta, and IGF-I receptor in the nucleus should be examined.

Animals↗
PubMed1992

Structural and functional evidence for activation of a chick retinoid X receptor by eicosanoids.

The retinoid X receptors (RXR-alpha, RXR-beta and RXR-gamma) are members of the steroid-thyroid hormone receptor superfamily of ligand-dependent transcription factors. They appear to function as auxiliary proteins that regulate high-affinity DNA binding and enhance transcriptional activity through heterodimer formation with other members of the superfamily. The RXR-alpha, RXR-beta and RXR-gamma proteins bind and are activated by the naturally occurring retinoid, 9-cis-retinoic acid. Structural similarities are apparent between retinoic acid and various eicosanoids, raising the possibility that eicosanoids may also activate retinoid receptors in vivo. We present evidence that lipoxygenase metabolites of arachidonic acid at submicromolar concentrations are capable of activating RXR-gamma activity in transient transfection assays. In addition, molecular modelling predicts conformational similarities between some lipoxygenase products and retinoic acid. Consistent with this, hydroxyeicosatetraenoic acids are known to mimic some actions of retinoids in cell-based assays. These observations raise the possibility that eicosanoids, already known to act both as local hormones and as intracellular second messengers, may also have a direct role in transcriptional activation via nuclear receptors.

Animals↗
PubMed1994

Endogenous retinoid X receptors can function as hormone receptors in pituitary cells.

Retinoids regulate gene transcription by interacting with both retinoic acid (RA) receptors (RARs) and retinoid X receptors (RXRs). Since unliganded RXRs can act as heterodimerization partners for RARs and other nuclear hormone receptors, it is unclear whether ligand binding by RXRs actually regulates the expression of naturally occurring genes. To address this issue, we synthesized the RXR-selective retinoid SR11237 and confirmed its specificity in transient transfection and proteolytic susceptibility assays before using it to assess the contribution of ligand-activated RXRs to retinoid action. Unlike RAR ligands, SR11237 did not increase endogenous RAR beta mRNA levels in F9 embryonal carcinoma cells, even though it activated transcription of an RXR-responsive reporter gene in these cells. Thus, it is likely that RARs mediate the induction of RAR beta gene expression by RA. In contrast, the RXR-specific ligand induced rat growth hormone mRNA in GH3 pituitary cells, indicating that the effects of RA on growth hormone gene expression at least in part involve ligand binding to endogenous RXRs in vivo. Our results indicate that in addition to serving as cofactors for other nuclear hormone receptors, endogenous RXRs can function as ligand-dependent regulators of gene expression, i.e., classical nuclear hormone receptors.

Animals↗
PubMed2000

Retinoids stimulate leptin synthesis and secretion in human syncytiotrophoblast.

The syncytiotrophoblast (ST), which forms the outer layer of the chorionic villi, is the endocrine unit of the human placenta. Bathing in the maternal blood of the intervillous space, the ST secretes its hormonal products directly into the maternal circulation. Leptin is expressed in the ST and is secreted into the maternal circulation. However, its regulation and physiological role during pregnancy remain poorly known. In the present work we used the in vitro model of human cytotrophoblast differentiation into ST to study the effect of physiological and synthetic retinoids on leptin synthesis and secretion. Using specific antibodies we first illustrated by immunocytochemistry the expression of retinoic acid (RA) receptor alpha and retinoid X receptor alpha (RXRalpha) in ST. We then observed that leptin messenger ribonucleic acid and protein expression increased with in vitro ST formation. The 9-cis isomer of RA and the synthetic retinoid specific for RXRs (BMS 649) stimulated leptin messenger ribonucleic acid expression and secretion. In contrast, all-trans-RA and a RA alpha-specific ligand had no effect. These results suggest that retinoids regulate leptin expression and highlight a role for RXRalpha in this process.

Adult↗
PubMed1997

Ligand-bound RXR can mediate retinoid signal transduction during embryogenesis.

Retinoids regulate various aspects of vertebrate development through the action of two types of receptors, the retinoic acid receptors (RARs) and the retinoid-X-receptors (RXRs). Although RXRs bind 9-cis-retinoic acid (9cRA) with high affinity, in vitro experiments suggest that RXRs are for the most part not liganded, but serve as auxiliary factors forming heterodimers with liganded partner receptors such as RAR. Here we have used RXR- and RAR-specific ligands 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-napthyl)ethenyl]b enzoic acid (LG69) and (E)-4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-1-prope nyl]benzoic acid (TTNPB), and show that, in the context of an embryo, liganded RXR can mediate retinoid signal transduction. This conclusion emerges from examining the induction of several retinoid-responsive genes in the limb bud (Hoxb-6/-8, RARbeta) and in the developing central nervous system (Hoxb-1, otx-2). RARbeta and Hoxb-1 genes were most effectively activated by a combination of TTNPB and LG69, suggesting that the activation of these genes benefits from the presence of ligand-bound RAR and ligand-bound RXR. Hoxb-6/-8 genes were most efficiently induced by LG69, suggesting that liganded RXR can activate these genes. The regulation of the expression of the otx-2 gene was complex; expression was repressed by TTNPB, but such repression was relieved when LG69 was provided together with TTNPB, suggesting that ligand-bound RXR can overcome repression of transcription exerted by liganded RAR. Based on these findings, we propose that in our experimental system in which ligands are provided exogenously, transcriptional regulation of several genes involves liganded RXR.

Animals↗
PubMed2005

Decreased expression of retinoid nuclear receptor (RAR alpha and RAR gamma) mRNA determined by real-time quantitative RT-PCR in peripheral blood mononuclear cells of hypothyroid patients.

In vivo assessment of the cellular impact of thyroid hormones on target tissues might be of help for physiological studies and to evaluate the consequences of various diseases of the thyroid gland in humans. Given the tenuous relationship between retinoid and tri-iodothyronine (T3) status and that retinoids have also intracellular roles, the aim of this study was to determine the effect of hypothyroidism on the expression of T3 nuclear receptors (TR) and retinoic acid nuclear receptors (RAR, RXR) in human peripheral blood mononuclear cells (PBMC). Using real time RT-PCR, we quantified the relative amount of mRNA of the thyroid (TR alpha and TR beta) and retinoid (RAR alpha, RAR gamma, and RXR alpha) nuclear receptors in PBMC of euthyroid (n = 22) compared with hypothyroid (n = 22) subjects. Classical plasma parameters (free T3 (FT3), free thyroxine (T4) (FT4), thyroid-stimulating hormone (TSH), retinol (ROH), retinol-binding protein (RBP) and transthyretin (TTR)) were also measured. In hypothyroid subjects, the concentration of TSH was elevated, and dramatically low T3 and T4 concentrations were associated with a decrease in the expression of TR beta. Expression of RAR alpha and RAR gamma significantly decreased in hypothyroid versus control subjects, while an increased concentration of ROH was emphasised by hypothyroidism. These results first indicated that primary hypothyroidism induces hypoactivation of the retinoid nuclear pathway in PBMC, which was not predicted by the plasma ROH level. Further investigations will be necessary to evaluate these parameters in very small changes in thyroid hormone production such as mild (subclinical) hypothyroidism.

Base Sequence↗
PubMed2005

The mechanism of action of topical retinoids.

UV irradiation of human skin sets in motion a complex sequence of events that causes damage to the dermal matrix. When topical tretinoin is applied to human skin, any collagen deficiency existing in photoaged skin is remedied at least partially, and the skin is primed to prevent further matrix degradation induced by solar UV. Retinoids, therefore, have become essential in the treatment and prevention of photoaging. This article describes the mechanism of action of retinoids, including how they are mediated through retinoic acid receptors (RARs) and retinoid X receptors (RXRs), how they block inflammation mediators, and how production of procollagen is increased to augment the formation of types I and III collagen. Three naturally occurring retinoids are reviewed.

Acne Vulgaris↗
PubMed1998

A high-risk lesion for invasive breast cancer, ductal carcinoma in situ, exhibits frequent overexpression of retinoid X receptor.

The development of prevention strategies for breast cancer will require a molecular map of carcinogenesis. We have investigated gene expression patterns in premalignant and early carcinomatous human breast lesions that confer to the patient varying risks for developing invasive breast cancer. The relative expression levels of one of the retinoid receptors, retinoid X receptor (RXR), was determined by in situ hybridization to 58 biopsy specimens; RXR mRNA grain density over each lesion was compared to that over the normal ductal/lobular units in each section. Overexpression of RXR mRNA was observed in 66% of noncomedo ductal carcinoma in situ (DCIS), which confer a >8-fold increase in breast cancer risk, and 88% of comedo DCIS lesions, which are associated with a yet higher risk. In contrast, only 8% of lesions that confer little or no increase in breast cancer risk overexpressed RXR mRNA (P = 0.0008). Limited in situ hybridization data using retinoic acid receptor (RAR) riboprobes showed overexpression of RAR alpha, but not RAR beta or -gamma, in only a modest percentage (36%) of cases, suggesting that all members of the retinoid receptor superfamily are not similarly regulated. Immunohistochemistry performed on 52 DCIS specimens for alpha, beta, and gamma isoforms of RXR confirmed its overexpression at the protein level and implicate RXR alpha as the predominant overexpressed form. The data indicate that RXR overexpression is associated with an increased risk for the development of invasive breast cancer in human breast lesions and suggest the hypothesis that it is causally involved in breast oncogenesis. The implications for retinoid chemoprevention are discussed.

Biomarkers, Tumor↗
PubMedDate not supplied

Activity of 9-cis-retinoic acid and receptor-selective retinoids in small cell lung cancer cell lines.

Dysregulation of retinoid signaling pathways appears to be an early event in the pathogenesis of small cell lung cancer (SCLC). We evaluated the activity of 9-cis-retinoic acid (9cRA), a pan- receptor agonist, and two synthetic retinoids, TTNPB and LG100153, which are RAR- and RXR- selective, respectively, against a panel of SCLC cell lines. LG100153 was the most potent agent with an IC50 < 1.0 microM in three cell lines. TTNPB had an IC50 < 1.0 microM in two lines, and 9cRA an IC50 < 1.0 microM in only one. By fluorescent microscopy, LG100153, TTNPB and 9cRA also induced morphologic evidence of apoptosis in three, two and one cell lines, respectively. Although the expression of RARs and RXRs varied widely between cell lines, there was no clear correlation between the level or pattern of receptor expression and retinoid activity. These data suggest that novel retinoids, especially RXR-selective agents, deserve further evaluation in the treatment of SCLC.

Alitretinoin↗
PubMed1996

Interferons induce normal and aberrant retinoic-acid receptors type alpha in acute promyelocytic leukemia cells: potentiation of the induction of retinoid-dependent differentiation markers.

Treatment of the acute promyelocytic (APL) cell line NB4 with interferon alpha (IFN(alpha)), as well as IFN(beta) and gamma, results in an increased expression of the transcripts coding for retinoic-acid receptor type alpha (RAR(alpha)) and the leukemia-specific retinoic acid receptor PML-RAR. Transcriptional induction of the RAR(alpha) and PML-RAR mRNAs is rapid and it is parallelled by an increase in the corresponding proteins. Up-regulation of RAR(alpha) and PML-RAR gene expression by IFN(alpha) is accompanied by a strong potentiation in the induction of 2 retinoid-dependent granulocytic markers, i.e., granulocyte-colony-stimulating factor receptor mRNA and leukocyte alkaline phosphatase. However, IFN(alpha) does not have any effects on the retinoid-dependent regulation of the myeloid surface markers CD11b and CD33. The IFN-dependent increase in RAR(alpha) levels and the enhancing effect of the cytokine on retinoid-dependent granulocytic markers expression may be a characteristic of PML-RAR positive cells, since the phenomena are not observed in HL-60 promyelocytes. Interferons as well as retinoids inhibit the growth of NB4 cells, although the 2 classes of compounds do not significantly interact in terms of anti-proliferative activity. These results suggest the possible use of combinations between IFNs and retinoic acid in the cyto-differentiating treatment of APL patients.

Alkaline Phosphatase↗
PubMed1997

Expression of the vitamin D and the retinoid X receptors in Saccharomyces cerevisiae: alternative in vivo models for ligand-induced transactivation.

The transcription factors of the nuclear hormone receptor family regulate gene expression via a complex network of macromolecular interactions. The ligand dependent activity of the vitamin D receptor is of particular interest because it modulates gene expression by the heterodimeric interaction with retinoid X receptors. We report here that individual functions of the vitamin D receptor including DNA-binding, homo- and heterodimerization and transactivation can be reconstituted in the yeast Saccharomyces cerevisiae. Interestingly, the simultaneous expression of the native vitamin D receptor and the retinoid X receptor beta resulted in a ligand independent transactivation of the lacZ reporter gene coupled to a mouse osteopontin vitamin D response element. However, homodimerization of the vitamin D receptor and heterodimerization were strongly enhanced upon ligand binding, when the receptors were expressed as fusion proteins with the Gal4 transcription factor in a yeast two-hybrid system. Furthermore, transactivating activity of a Gal4-fused vitamin D receptor was induced by vitamin D in a one-hybrid system devoid of retinoid X receptors. In addition, both Gal4-based systems behaved similar with regard to their dose-dependent response to vitamin D and related compounds when compared to the transcriptional activity of the vitamin D receptor in transiently transfected MCF-7 cells. Our results point out that specific ligands strongly enhanced receptor dimerization and induced transactivation in yeast and in MCF-7 cells. The constitutive transactivation by vitamin D receptor-retinoid X receptor heterodimers in yeast, depending on DNA binding of the receptors, strongly argues for the existence of cofactors, which are absent in yeast, but play a fundamental role in gene regulation in higher eukaryotic organisms.

Animals↗
PubMed1985

Inhibition by retinoids of neoplastic transformation in vitro: cellular and biochemical mechanisms.

We have demonstrated that non-toxic concentrations of retinoids can cause a dose-dependent inhibition of 3-methylcholanthrene-induced transformation of C3H/10T1/2 cells. On removal of the retinoid, transformed foci appear after a latent period of about four weeks at the same frequency as observed in controls treated with carcinogen only. Reasoning that this activity is compatible with the stabilization of the carcinogen-initiated state, we have succeeded in isolating from carcinogen-treated cultures a cell line which in the presence of retinyl acetate is similar to the parental 10T1/2 cells, but without retinyl acetate transforms at a high frequency after a latent period of about four weeks. Retinyl acetate treatment of this cell line (INIT/10T1/2) and the parental 10T1/2 cells induces an ultra-normal phenotype. In retinoid-deprived INIT/10T1/2 cells, the first sign of transformation (an increased thymidine-labelling index) occurs 16 days after retinyl acetate removal. We have detected by two-dimensional electrophoresis that concomitant with this there is an increase in phosphorylation of a protein of Mr 34 000 (34K) which may be associated with the cytoskeleton. This phosphoprotein has been found in all transformed lines examined. A second phosphoprotein, of about 38K, has also been detected in transformed cells. Retinyl acetate treatment of transformed cells alters the isoelectric point of this protein, a change compatible with decreased phosphorylation. Alkali-resistant phosphorylation, presumably on tyrosine, has been found on a second 34K protein of transformed cells. Retinyl acetate treatment specifically decreases this phosphorylation. Mechanisms for the altered tyrosine phosphorylation induced by retinyl acetate are as yet unresolved, but the decrease could be due to altered levels of substrate, kinase or phosphorylase. In view of the apparent role of tyrosine kinases as mediators of growth factors and as oncogene products, we consider the activity of retinoids as modulators of tyrosine phosphorylation to be of great potential significance.

Animals↗
PubMed2006

Synthesis and antioxidant activity of new tetrahydro-naphthalene-indole derivatives as retinoid and melatonin analogs.

A number of retinoid-related compounds represent classes of antioxidative and proapoptotic agents with promising potential in the treatment of neoplastic diseases. Indeed, the synthetic retinoid amide fenretinide [N-(4-hydroxyphenyl)retinamide] induces apoptosis of cancer cells and acts as a chemotherapeutic drug in cancer therapy. In the present work, and as a continuation of our studies on retinoid-type compounds, the synthesis of melatonin retinamide derivatives was studied as a novel series of melatonin retinoids, using the condensation reaction sequence involving tetrahydrotetramethylnaphthalene carboxylic acid and appropriate melatonin-type moieties. Despite of the weak DPPH inhibition activity pattern of the synthesized compounds, some of them showed a strong inhibition on lipid peroxidation (IVa-b, Va, and VIIa-c, 88, 96, 90, 94, 93, and 86%, respectively at 10(-4) M concentration) when melatonin (85% at 10(-4) M concentration) was used as a reference compound.

Animals↗
PubMed1987

Procollagen gene expression by scleroderma fibroblasts in culture. Inhibition of collagen production and reduction of pro alpha 1(I) and pro alpha 1(III) collagen messenger RNA steady-state levels by retinoids.

Recent studies have demonstrated that retinoids (synthetic vitamin A analogs) can modulate connective tissue metabolism in human skin fibroblast cultures. In this study, we examined the effects of 3 retinoids, all-trans-retinoic acid (RA), 13-cis-RA, and an aromatic retinoid, RO-10-9359, on collagen gene expression in scleroderma fibroblast cultures and matched control fibroblast cultures. The results indicated that all-trans-RA and 13-cis-RA significantly reduced procollagen production both in control and scleroderma fibroblast cultures in a dose-dependent manner. The reduction in procollagen production was paralleled by a similar decrease in steady-state levels of type I and type III procollagen messenger RNAs, which suggests that there is coordinate inhibition on the transcriptional level. In contrast, RO-10-9359 elicited only limited effects on collagen production, and such effects were variable. The results suggest that further development of retinoids might provide an effective means to counteract tissue deposition of collagen in scleroderma and other fibrotic diseases.

Adult↗
PubMed1994

Synergistic effect of retinoids and interferon alpha on tumor-induced angiogenesis: anti-angiogenic effect on HPV-harboring tumor-cell lines.

Various retinoids and interferons exert anti-tumor effects both in experimental studies and in clinical trials. Recent reports indicate that they have a synergistic antineoplastic activity. Our study aimed to determine whether these synergistic anti-tumor effects are related to inhibition of tumor-cell-induced angiogenesis. A further aim was to compare the anti-angiogenic activity of various retinoids including 9-cis retinoic acid, a ligand for nuclear retinoic acid receptor RXR, given alone and in combination with interferon alpha-2a (IFN alpha-2a). An in vivo experimental model of cutaneous angiogenesis in the mouse was used. Angiogenesis was induced by intradermal injection of HPV16- or HPV18 DNA-harboring tumor-cell lines. All-trans retinoic acid (all-trans RA), 13-cis retinoic acid (13-cis RA) and 9-cis retinoic acid (9-cis RA) as well as IFN alpha-2a applied to mice intraperitoneally for 5 consecutive days before induction of angiogenesis resulted in significant inhibition of angiogenesis. Combination of retinoids with IFN alpha-2a led to a synergistic inhibition of angiogenesis, as compared to the effects of the drugs given alone. Similar results were obtained when tumor cells were preincubated in vitro with the compounds, before injection into untreated mice. Our findings on synergistic anti-angiogenic effects of retinoids and IFN alpha-2a could explain, at least partially, the anti-tumor efficacy of combined therapy with these agents, and provide support for the role of angiogenesis in tumor growth.

Animals↗
PubMed1994

Characterization of heterologously expressed recombinant retinoic acid receptors with natural or synthetic retinoids.

The first step in retinoid action is binding to their nuclear receptors. Therefore, characterization of binding characteristics of retinoids is of major importance. Human retinoic acid receptors alpha (hRAR alpha), hRAR beta, and mouse RAR gamma (mRAR gamma) were expressed heterologously in Escherichia coli as a recombinant glutathione S-transferase (GST) fusion protein. The expressed fusion proteins were functional and bound specifically to the all-trans-retinoic acid (RA). The dissociation constants (Kd) for RA were 1.4 nM for GST-hRAR alpha, 1.4 nM for GST-hRAR beta, and 3.3 nM for GST-mRAR gamma, respectively. The fusion proteins were further used for competitive displacement assays to determine the displacement constant (DC50) for other selected retinoids. All-trans-RA and 4-oxo-all-trans-RA have high affinity with all three receptors (DC50 = 0.8-55 nM). The 13-cis RA binds to hRAR alpha with low affinity, but not to other RARs evaluated here. All-trans-N-ethylretinamide, all-trans-retinylacetate, and an ethyl ester of tetrahydronaphthalene derivative had no affinity to any RARs. The hRAR alpha and mRAR gamma receptors did not bind a naphthalene carboxylic acid derivative of RA, but hRAR beta binds this chemical with high affinity. Results indicated that the three recombinant proteins were functional in binding various RA congeners. The affinity and binding data of these retinoids were compared to their observed teratogenic activity.

Amino Acid Sequence↗
PubMed1993

Squamous cell differentiation markers in normal, premalignant, and malignant epithelium: effects of retinoids.

Vitamin A and some of its analogs (retinoids) maintain normal differentiation of epithelial tissues by preventing aberrant squamous differentiation of cells in nonkeratinizing epithelia. They can also reverse squamous metaplasia, which develops in vivo during vitamin A deficiency. These effects are the result of the ability of retinoids to suppress the expression of genes associated with squamous differentiation (e.g., transglutaminase type I, loricrin, involucrin, filaggrin, and keratin K1). In addition, retinoids reverse keratinizing premalignant lesions in the oral cavity, and inhibit the growth and squamous differentiation of head and neck squamous cell carcinomas (HNSCCs) in vitro. Nuclear retinoic acid receptors, which function as DNA-binding, trans-acting, transcription-modulating factors, are considered to be the proximate mediators of the effects of retinoids on gene expression and may mediate the re-regulation of aberrant differentiation and growth of premalignant and some malignant cells, thereby suppressing the development of head and neck cancer.

Animals↗