ライフサイエンスコーパス: RAR beta

1 RAR-beta expression was weak or absent in normal and les

2 RAR-beta may suppress tumorigenicity.

3 RAR-beta mRNA expression was undetectable in 51 patients

4 RAR-beta mRNA is undetectable by in situ hybridization (

5 RAR-beta was detected in 88% (14/16) of normal esophagea

6 RAR-beta, COX-2, and hTERT mRNA levels were determined b

7 RAR-beta/gamma and anti-AP-1-selective retinoids, but no

8 .01), MINT25 (P = 0.01), MINT27 (P = 0.001), RAR beta (P = 0.03), and ER (P = 0.001), and than ampull

9 in various combinations of the RAR alpha 1, RAR beta, and RXR alpha gene mutations.

10 ce in the genes that encode the RAR alpha 1, RAR beta, and RXR alpha retinoic acid receptors as a mea

11 eceptor (ER), retinoic acid receptor beta 2 (RAR beta), and T-type calcium channel (CACNA1G) genes, a

12 f hormone-dependent cells was inhibited by a RAR beta-selective antagonist and the expression of RAR

13 Our findings implicate a RAR-beta/MLC-2 pathway in peritumoural stromal remodelli

14 han for the 115 patients with weak or absent RAR-beta (P =.045).

15 also unable to induce COX-2 expression after RAR-beta(2) expression was manipulated in these esophage

16 While RAR alpha, RAR beta, and RAR gamma are expressed in distinct but ov

17 Thus, AGN193109, which binds to RAR alpha, RAR beta, and RAR gamma with Kd values = 2,2, and 3 nm,

18 l-trans retinoic acid in mammals, RAR alpha, RAR beta, and RAR gamma, which transduce the retinoic ac

19 ll surface antigen CD7 and either RAR alpha, RAR beta, RAR gamma, or RXR alpha.

20 RAR-alpha, RAR-beta, and RAR-gamma mRNAs were expressed in all 20 a

21 p junctional channels is mediated through an RAR(beta)(/gamma)-like binding site.

22 cid receptor agonists (CD271 = adapalene, an RAR-beta,gamma agonist; CD2043 = retinoic acid receptor

23 We retrospectively analyzed RAR-beta mRNA levels (by ISH using a digoxigenin-labeled

24 tal ventricular defects, the RAR alpha 1 and RAR beta mutations are apparently nonphenotypic in the h

25 d, whereas RAR gamma was less effective, and RAR beta was ineffective.

26 decreased by a mean of 28.8% (P = 0.01), and RAR-beta levels were increased by a mean of 60% (P = 0.0

27 lls, whereas the expression of RAR-alpha and RAR-beta was not observed in any cell line.

28 ne expression levels of EGFR, TGF-alpha, and RAR-beta before and after treatment with LGD1069 (10 mic

29 omarker genes including TGF-alpha, EGFR, and RAR-beta in seven SCCHN cell lines.

30 f tumor suppressor genes such as RASSF1A and RAR-beta, which are frequently silenced in human lung ca

31 ween the expression of estrogen receptor and RAR-beta.

32 The methylation of TIG1 and RAR-beta was positively correlated (r=0.35; P=0.017).

33 ARalpha) associated with the Sp1 region, and RARs beta and gamma associated with the AP-1 and Sp1 reg

34 Antisense RAR-beta-transfected TE-3 cells had a shorter doubling t

35 ageal cancer cell line TE-8 and an antisense RAR-beta into TE-3 cells.

36 ta transfected TE-8 cells, whereas antisense RAR-beta transfected TE-3 cells increased COX-2 expressi

37 P = 0.001), and than ampullary carcinomas at RAR beta (P = 0.02) and ER (P = 0.03).

38 Retinoic acid receptor-beta (RAR beta) and signal transducer and activator of transcr

39 vels, increases retinoic acid receptor-beta (RAR beta) mRNA levels, suppresses proliferation, and alt

40 The retinoic acid receptor beta (RAR-beta) gene was frequently methylated as well (42/50,

41 disease (VHL), retinoic acid receptor beta (RAR-beta), RAS association domain family 1A (RASSF1A), a

42 ism involving a retinoic acid receptor beta (RAR-beta)-dependent downregulation of actomyosin (MLC-2)

43 A-induced up-regulation of RA receptor beta (RAR-beta).

44 wn to suppress retinoic acid receptor-beta2 (RAR-beta(2)) and induce cyclooxygenase-2 (COX-2) express

45 Expression of both RAR beta and STAT1 is lost in most breast cancer cell li

46 gamma remains positive in HEC specimens, but RAR-beta expression was detected in only 6 of 20 HEC spe

47 of nine TSGs (SOCS-1, GSTP, APC, E-cadherin, RAR-beta, p14, p15, p16, and p73) in 51 cases of HCC usi

48 Among esophageal carcinomas RAR-beta mRNA was expressed in 62% (26/42) of well-diffe

49 In contrast, RAR-beta was expressed in five of seven cell lines and u

50 In contrast, RAR-beta was expressed in only 57% (17/30) of dysplastic

51 Methylated alleles of Cyclin D2, RAR-beta, and Twist genes were frequently detected in fl

52 l keratinocytes stably overexpressing either RAR beta or RAR alpha were generated by defective retrov

53 d when a combination of RXR-alpha and either RAR-beta or RAR-gamma was overexpressed in SK-OV3 cells.

54 accomplished by the induction of endogenous RAR beta expression.

55 esophageal cancer cells that do not express RAR-beta are resistant to retinoic acid (RA), we stably

56 Cell lines that did not express RAR-beta were also resistant to RA.

57 Esophageal cancer cells that do not express RAR-beta(2) did not respond to BPDE for induction of COX

58 Two cell lines that failed to express RAR-beta showed no growth inhibition or apoptosis and no

59 decreases in the number of cases expressing RAR-beta were observed among ductal carcinoma in situ (8

60 ression, COX-2 expression, hTERT expression, RAR-beta expression, and K-ras mutations were observed i

61 retinal horizontal cells through an external RAR(beta)(/gamma)-like binding site, the action of which

62 nd APC, 29% for CDH13, 16% for FHIT, 15% for RAR beta, 11% for GSTP1, 7% for p16(INK4A), 4% for DAPK,

63 for E-cadherin, 25.9% for p16, and 27.5% for RAR-beta(2).

64 we investigated the molecular mechanisms for RAR-beta(2)-mediated suppression of COX-2 expression usi

65 This closed helix 12 conformation in RAR beta and RAR gamma blocks corepressor binding, preve

66 These results implicate decreases in RAR-beta expression in breast cancer development and sug

67 on of RAR-beta decreased COX-2 expression in RAR-beta transfected TE-8 cells, whereas antisense RAR-b

68 linical stages I and II, hypermethylation in RAR-beta (67%) and FHIT (78%) was frequently detected, w

69 ng noncancerous tissues, hypermethylation in RAR-beta and FHIT was frequently detected in 38 and 30%,

70 f ciglitazone and SR11237 was able to induce RAR beta in all-trans-retinoic acid-resistant MDA-MB-231

71 tazone, but not 15d-PGJ(2), strongly induced RAR beta expression in human breast and lung cancer cell

72 receptor subtype, as ATRA remarkably induced RAR-beta mRNA levels, whereas RAR-beta knockdown substan

73 When TIG1 showed methylation, RAR-beta was also methylated (25/26 samples).

74 inoids is conditional, and levels of neither RAR beta nor RAR alpha are limiting to the intrinsic mec

75 wed no growth inhibition or apoptosis and no RAR-beta inducibility.

76 l synapses by activation of novel nonnuclear RAR(beta)(/gamma)-like sites either directly on, or inti

77 rved when RAR-alpha and/or RXR-alpha but not RAR-beta or RAR-gamma expression vectors are cotransfect

78 se studies indicate the existence of a novel RAR beta-mediated signaling pathway of PPAR gamma action

79 We show that activation of RAR beta, but not alpha, induces expression of the fibro

80 ntributes to the growth-inhibitory effect of RAR beta.

81 compensatory increases in the expression of RAR beta and RAR gamma proteins.

82 a-selective antagonist and the expression of RAR beta antisense RNA.

83 Our data demonstrate that induction of RAR beta by RA correlates with the growth-inhibitory eff

84 The induction of RAR beta expression by the ciglitazone and SR11237 combi

85 e element and the retinoic acid induction of RAR beta expression.

86 ls; this process required the involvement of RAR beta and protein synthesis.

87 The direct involvement of RAR beta in atRA-induced STAT1 gene activation was furth

88 ccharomyces cerevisiae, for the isolation of RAR beta mutants that have gained the RAR alpha-like cor

89 We tested the hypothesis that the level of RAR beta expressed by a keratinocyte determines its K19

90 Despite expressing abundant levels of RAR beta mRNA, lung adenocarcinoma H1792 cells are resis

91 Loss of RAR beta, therefore, may contribute to the tumorigenicit

92 enic mice, which resulted in upregulation of RAR beta and RAR gamma, can be associated with lymphomag

93 data demonstrated that anticancer effect of RAR-beta may be related to its ability to suppress COX-2

94 The inhibitory effect of RAR-beta on COX-2 expression was further enhanced in the

95 , we hypothesized that loss of expression of RAR-beta gene in stage I NSCLC is a prognostic factor of

96 These data suggest that the expression of RAR-beta is associated with response of HEC cells to RA

97 To explore the expression of RAR-beta mRNA in vivo, we analyzed esophageal tissue spe

98 onstrated that BPDE-suppressed expression of RAR-beta(2) results in COX-2 induction and restoration o

99 ponse to the methylation and inactivation of RAR-beta.

100 Induction of RAR-beta decreased COX-2 expression in RAR-beta transfec

101 d COX-2 expression was through inhibition of RAR-beta(2) and consequently, induction of epidermal gro

102 ce after an extended lifespan showed loss of RAR-beta and p16INK4A/p14ARF expression, but retained fu

103 Our data suggest that the loss of RAR-beta expression is an early event associated with es

104 onse of HEC cells to RA and that the loss of RAR-beta expression may be associated with HEC developme

105 OX-2 expression and support that the loss of RAR-beta expression may contribute to esophageal carcino

106 , BPDE induced time-dependent methylation of RAR-beta(2) gene promoter in esophageal cancer cells.

107 esults in COX-2 induction and restoration of RAR-beta(2) expression reduces COX-2 protein in esophage

108 Restoration of RAR-beta(2) inhibited growth and colony formation of eso

109 I-beta-mediated transcriptional silencing of RAR-beta Notably, EAD was the most effective combination

110 Transfection of RAR-beta decreased cell growth and colony formation and

111 Transfection of RAR-beta(2) expression vector into esophageal cancer cel

112 In addition, co-treatment of RAR-beta(2)-positive cells with BPDE and the MEK1/2 inhi

113 of RARalpha and decreased the association of RARs beta and gamma.

114 al of the 41 patients with strongly positive RAR-beta was significantly worse than for the 115 patien

115 do not express the retinoid nuclear receptor RAR beta and RAR gamma and express a truncated RAR alpha

116 element of the beta-retinoic acid receptor (RAR beta) gene, as well as to other related DNA elements

117 how here the role of retinoic acid receptor (RAR) beta and alpha signalling in proliferation and diff

118 subtypes express the retinoic acid receptor (RAR) beta at levels roughly correlated with their level

119 wth and induction of retinoic acid receptor (RAR) beta expression in breast and lung cancer cells.

120 d by its blockade of retinoic acid receptor (RAR) beta expression induced by the RXRalpha/peroxisome

121 CYP26A1 and retinoic acid receptor (RAR) beta were found to be greatly inducible by atRA in

122 our changes: loss of retinoic acid receptor (RAR)-beta and p16INK4A expression, p53 mutations and act

123 lines do not express retinoic acid receptor (RAR)-beta in response to all-trans retinoic acid (RA) be

124 Since retinoic acid receptor (RAR)-beta mRNA is frequently lost during esophageal carc

125 tic silencing of the retinoic acid receptor (RAR)-beta The histone deacetylase inhibitor entinostat i

126 are as effective as retinoic acid receptor (RAR)-beta/gamma-selective compounds.

127 Retinoic acid receptor (RAR)beta is perceived to function as a tumor suppressor

128 y, the expression of retinoic acid receptor (RAR-beta) and retinoid X receptors (RXR-beta, -gamma) wa

129 otein and transcript levels, it up-regulated RAR beta transcripts, and it had no effect on RAR gamma.

130 ypical mortal dyplasia cultures (that retain RAR-beta and p16INK4A expression) does not extend their

131 Selective RAR(beta)(/gamma) ligands, but not an RAR(alpha)-selecti

132 showing that transfection with an anti-sense RAR beta construct blocked atRA-induced STAT1 expression

133 MCF-7 cells whereas introduction of a sense-RAR beta construct resulted in STAT1 induction by atRA i

134 These derivatives, in general, showed RAR beta,gamma selectivity.

135 n and restoration of epigenetically silenced RAR-beta expression.

136 be comparable to retinoic acid and slightly RAR beta,gamma selective.

137 Unexpectedly, strong RAR-beta expression was associated with a significantly

138 wo mediators and present evidence supporting RAR beta as a tumor suppressor.

139 or-selective retinoids, we demonstrated that RAR beta induction in MCF-7 cells by all-trans-retinoic

140 further supporting our previous finding that RAR-beta(2) plays an important role in suppressing esoph

141 As a consequence, the RAR beta and RAR gamma receptors appear to adopt a const

142 (beta retinoic acid response element) in the RAR beta promoter.

143 n that the tissue-specific expression of the RAR beta 2 gene in mouse embryos is regulated at the tra

144 is necessary for appropriate response of the RAR beta and RAR gamma genes to physiologic changes and

145 tain overall RA signaling, and to refine the RAR beta effects in the lung field.

146 ndent cells acquired RA sensitivity when the RAR beta expression vector was introduced and expressed

147 Furthermore, the RAR-beta,gamma antagonist CD2665 antagonized the suppres

148 nd prostaglandin E(2) production only in the RAR-beta positive cells.

149 indings suggest that hypermethylation of the RAR-beta and FHIT may play an important role in the earl

150 A expression appeared to be mediated via the RAR-beta receptor subtype, as ATRA remarkably induced RA

151 l agent by increasing DRA expression via the RAR-beta/HNF-1beta-dependent pathway.

152 nfirmed that ATRA exerts its effects through RAR-beta.

153 Thus, RAR beta can mediate retinoid action in breast cancer ce

154 ees of selectivity for RAR alpha relative to RAR beta/gamma, with compound 5 being the most selective

155 tinamide, which does not bind effectively to RAR-beta, had no effect on COX-2 suppression.

156 to retinoic acid (RA), we stably transfected RAR-beta expression vector into an esophageal cancer cel

157 In primary tumors, hypermethylation in VHL, RAR-beta, RASSF1A, and FHIT was detected in 13, 55, 51,

158 Hypermethylation in VHL, RAR-beta, RASSF1A, and FHIT was detected in 36, 73, 73,

159 In almost all samples where RAR-beta was not methylated, TIG1 was also in an unmethy

160 in the c-jun-transfected MCF7 cells, whereas RAR beta expression was up-regulated.

161 n repress target gene transcription, whereas RAR beta and -gamma interact with SMRT only weakly and f

162 rkably induced RAR-beta mRNA levels, whereas RAR-beta knockdown substantially attenuated the ability