Retinoid targets for the treatment of cancer

Critical Reviews in Eukaryotic Gene Expression

Volumn 16, Issue 3, 2006, Pages 193-210

  Buletic, Zivjena ^a   Soprano, Kenneth J ^a   Soprano, Dianne Robert ^a  

^a TEMPLE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Cancer therapeutics; RAR; Retinoic acid; Rexinoids; RXR

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; 6 [3 (1 ADAMANTYL) 4 HYDROXYPHENYL] 2 NAPHTHOIC ACID; ANHYDRORETINOL; ANTINEOPLASTIC AGENT; ARSENIC TRIOXIDE; BUTYRIC ACID; CELL NUCLEUS RECEPTOR; FENRETINIDE; HISTONE DEACETYLASE INHIBITOR; LIAROZOLE; MX 3350 1; N [4 [2 ETHYL 1 (1H 1,2,4 TRIAZOL 1 YL)BUTYL]PHENYL] 2 BENZOTHIAZOLAMINE; NAPHTHALENE DERIVATIVE; NAPHTHOIC ACID DERIVATIVE; OXYGENASE; R 116010; RETINOIC ACID; RETINOIC ACID 4 HYDROXYLASE; RETINOIC ACID DERIVATIVE; RETINOIC ACID RECEPTOR; RETINOIC ACID RECEPTOR ALPHA; RETINOIC ACID RECEPTOR BETA; RETINOID; RETINOID DERIVATIVE; RETINOID X RECEPTOR; RETINOL ESTER; REXINOID; TRICHOSTATIN A; UNCLASSIFIED DRUG; VN 14;

ACUTE GRANULOCYTIC LEUKEMIA; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; BREAST CANCER; CANCER CHEMOTHERAPY; CARCINOGENESIS; CELL NUCLEUS; CLINICAL TRIAL; DEGRADATION KINETICS; DNA METHYLATION; DRUG SAFETY; DRUG TARGETING; ENZYME ACTIVITY; ENZYME INHIBITION; ESOPHAGUS CANCER; HEAD AND NECK CANCER; HUMAN; LUNG CANCER; MOUTH CANCER; NONHUMAN; OVARY CANCER; OXIDATIVE STRESS; PRIORITY JOURNAL; PROMYELOCYTIC LEUKEMIA; REVIEW; SIGNAL TRANSDUCTION; UTERINE CERVIX CANCER; VITAMIN METABOLISM;

EID: 33749315480     PISSN: 10454403     EISSN: None     Source Type: Journal    
DOI: 10.1615/CritRevEukarGeneExpr.v16.i3.10     Document Type: Review

References (155)

1. Harrison EH. Mechanisms of digestion and absorption of dietary vitamin A. Annu Rev Nutr. 2005;25:87-103.
2. Ross AC, Zolfaghari R, Weisz J. Vitamin A: recent advances in the biotransformation, transport, and metabolism of retinoids. Curr Opin Gastroenterol. 2001;17(2):184-92.
3. Noy N. Retinoid-binding proteins: mediators of retinoid action. Biochem J. 2000;348 (Pt 3):481-95.
4. Napoli JL. Retinoic acid: its biosynthesis and metabolism. Prog Nucleic Acid Res Mol Biol. 1999;63:139-88.
5. Miller WH Jr. The emerging role of retinoids and retinoic acid metabolism blocking agents in the treatment of cancer. Cancer. 1998;83(8):1471-82.
6. Njar VC. Cytochrome p450 retinoic acid 4-hydroxylase inhibitors: potential agents for cancer therapy. Mini Rev Med Chem. 2002;2(3):261-9.
7. Petkovich PM. Retinoic acid metabolism. J Am Acad Dermatol. 2001;45(5):S136-42.
8. Guo X, Ruiz A, Rando RR, Bok D, Gudas LJ. Esterification of all-trans-retinol in normal human epithelial cell strains and carcinoma lines from oral cavity, skin and breast: reduced expression of lecithin:retinol acyltransferase in carcinoma lines. Carcinogenesis. 2000;21:1925-33.
9. Guo Z, Nanus DM, Ruiz A, Rando RR, Bok D, Gudas LJ. Reduced levels of retinyl esters and vitamin A in human renal cancers. Cancer Res. 2001;61:2774-81.
10. Guo Z, Knudsen BS, Peehl DM, Ruiz A, Bok D, Rando RR, Rhim JS, Nanus DM, Gudas LJ. Retinol metabolism and lecithin:retinol acyltransferase levels are reduced in cultured human prostate cancer cells and tissue specimens. Cancer Res. 2002;62:1654-61.
11. Zhan HC, Gudas LJ, Bok D, Rando R, Nanus DM, Tickoo SK. Differential expression of the enzyme that esterifies retinol, lecithin:retinol acyltransferase, in subtypes of human renal cancer and normal kidney. Clin Cancer Res. 2003;9:4897-905.
12. Boorjian S, Tickoo SK, Mongan NP, Yu H, Bok D, Rando RR, Nanus DM, Scherr DS, Gudas LJ. Reduced lecithin:retinol acyltransferase expression correlates with increased pathologic tumor stage in bladder cancer. Clin Cancer Res. 2004;10:3429-37.
13. Kuppumbatti YS, Bleiweiss IJ, Mandeli JP, Waxman S, Mira-y-Lopez R. Cellular retinol-binding protein expression and breast cancer. J Natl Cancer Inst. 2000;92:475-80.
14. Jeronimo C, Oliveira HR, Lobo F, Pais I, Teixeira MR, Lopes C. Aberrant cellular retinol binding protein 1 (CRBP1) gene expression and promoter methylation in prostate cancer. J Clin Pathol. 2004;57:872-6.
15. Kuppumbatti YS, Rexer B, Nakajo S, Nakaya K, Mira-y-Lopez R. CRBP suppresses breast cancer cell survival and anchorage-independent growth. Oncogene. 2001;20:7413-9.
16. Esteller M, Guo M, Moreno V, Peinado MA, Capella G, Galm O, Baylin SB, Herman JG. Hypermethylation-associated inactivation of the cellular retinol-binding protein 1 gene in human cancer. Cancer Res. 2002;62:5902-5.
17. Arapshian A, Bertran S, Kuppumbatti YS, Nakajo S, Mira-y-Lopez R. Epigenetic CRBP downregulation appears to be an evolutionarily conserved (human and mouse) and oncogene-specific phenomena in breast cancer. Mol Cancer. 2004;3:13.
18. Farias EF, Ong DE, Ghyselinch NB, Nakajo S, Kuppumbatti YS, Mira-y-Lopez R. Cellular retinol-binding protein I, a regulator of breast epithelial retinoic acid receptor activity, cell differentiation, and tumorigenicity. J Natl Cancer Inst. 2005;97:21-9.
19. Simmons DP, Peach ML, Friedman JR, Green MM, Nicklaus MC, De Luca LM. Evidence that sequence homologous region in LRAT-like proteins possesses anti-proliferative activity and DNA binding properties: translational implications and mechanism of action. Carcinogenesis. Epub October 18, 2005.
20. Budh AS, Noy N. Direct channeling of retinoic acid between cellular retinoic acid-binding protein II and retinoic acid receptor sensitizes mammary carcinoma cells to retinoic acid-induced growth arrest. Mol Cell Biol. 2002;22:2632-41.
21. Vo HP, Crowe DL. Transcriptional regulation of retinoic acid responsive genes by cellular retinoic acid binding protein-II modulates RA mediated tumor cell proliferation and invasion. Anticancer Res. 1998;18:217-24.
22. Donato LJ, Noy N. Suppression of mammary carcinoma growth by retinoic acid: proapoptotic genes are targets for retinoic acid receptor and cellular retinoic acid-binding protein II signaling. Cancer Res. 2005;65:8193-9.
23. Van Wauwe JP, Coene MC, Goossens J, Van Nijen G, Cools W, Lauwers W. Ketoconazole inhibits the in vitro and in vivo metabolism of all-trans-retinoic acid. J Pharmacol Exp Ther. 1988;245:718-22.
24. Van Wauwe JP, Coene MC, Goossens J, Cools W, Monbaliu J. Effects of cytochrome P-450 inhibitors on the in vivo metabolism of all-trans-retinoic acid in rats. J Pharmacol Exp Ther. 1990;252:365-9.
25. Van Wauwe J, Van Nyen G, Coene MC, Stoppie P, Cools W, Goossens J, Borghgraef P, Janssen PA. Liarozole, an inhibitor of retinoic acid metabolism, exerts retinoid-mimetic effects in vivo. J Pharmacol Exp Ther. 1992;261:773-9.
26. Van Ginckel R, DeCoster R, Wouters W, Vanherck W, van DerVeer R, Goeminne N, Jagers E, van Canteren H, Wouters L, Gistelmans W, Janssen PAJ. Antitumoral effects of R 75251 on the growth of transplantable R3327 prostatic adenocarcinoma in rats. Prostate. 1990;16:313-23.
27. DeCoster R, Wouters W, Van Ginckel R, End D, Krekels M, Coene MC, Dowden C. Experimental studies with liarozole (R 75,251): an antitumoral agent which inhibits retinoic acid breakdown. J Steroid Biochem Mol Biol. 1992;43:197-201.
28. Stearns ME, Wang M, Fudge K. Liarozole and 13-cis-retinoic acid anti-prostatic tumor activity. Cancer Res. 1993; 53:3073-7.
29. Smets G, Van Ginckel R, Daneels G, Moeremans M, Van Wauwe J, Coene MC, Ramaekers FC, Schalken JA, Borgers M, De Coster R. Liarozole, an antitumor drug, modulates cytokeratin expression in the Dunning AT-6sq prostatic carcinoma through in situ accumulation of all-trans-retinoic acid. Prostate. 1995;27:129-40.
30. Van Heusden J, Borgers M, Ramaekers F, Khonneux B, Wouters W, De Coster R, Smets G. Liarozole potentiates the all-trans-retinoic acid-induced structural remodelling in human breast carcinoma MCF-7 cells in vitro. Eur J Cell Biol. 1996;71:89-98.
31. Van Heusden J, Wouters W, Ramaekers FC, Krekels MD, Dillen L, Borgers M, Smets G. The antiproliferative activity of all-trans-retinoic acid catabolites and isomers is differentially modulated by liarozole-fumarate in MCF-7 human breast cancer cells. Br J Cancer. 1998;77:1229-35.
32. Njar VC, Nnane IP, Brodie AM. Potent inhibition of retinoic acid metabolism enzyme(s) by novel azolyl retinoids. Bioorg Med Chem Lett. 2000;10:1905-8.
33. Patel JB, Huynk CK, Handratta VD, Gediya LK, Brodie AM, Goloubeva OG, Clement OO, Nanne IP, Soprano DR, Njar VC. Novel retinoic acid metabolism blocking agents endowed with multiple biological activities are efficient growth inhibitors of human breast and prostate cancer cells in vitro and a human breast tumor xenograft in nude mice. J Med Chem. 2004;47:6716-29.
34. Van Heusden J, Van Ginckel R, Bruwiere H, Moelans P, Janssen B, Floren W, van der Leede BJ, van Dun J, Sanz G, Venet M, Dillen L, Van Hove C, Willemsens G, Janicot M, Wouters W. Inhibition of all-TRANS-retinoic acid metabolism by R116010 induces antitumor activity. Br J Cancer. 2002;86:605-11.
35. Stoppie P, Borgers M, Borghgraef P, Dillen L, Goossens J, Sanz G, Szel H, Van Hove C, Van Nyen G, Nobels G, Vanden Bossche H, Venet M, Willemsens G, Van Wauwe J. R1158566 inhibits all-trans-retinoic acid metabolism and exerts retinoidal effects in rodents. J Pharmacol Exp Ther. 2000;293:304-12.
36. Yee SW, Jarno L, Gomaa MS, Elford C, Ooi LL, Coogan MP, McClelland R, Nicholson RI, Evans BA, Brancale A, Simons C. Novel tetralone-derived retinoic acid metabolism blocking agents: synthesis and in vitro evaluation with liver microsomal and MCF-7 CYP26A1 cell assays. J Med Chem. 2005;48:7123-31.
37. Mulvihill MJ, Kan JLC, Beck P, Bittner M, Cesario C, Cooke A, Keane DM, Nigro AI, Nillson C, Smith V, Srebernak M, Sun F-L, Vrkljan M, Winski SL, Castelhano AL, Emerson D, Gibson N. Potent and selective [2-imidazol-1-yl-2-(6- alkoxynaphthalen-2-yl)-1-methyl-ethyl]-dimethyl-amines as retinoic acid metabolic blocking agents (RAMBAs). Bioorg Med Chem Lett. 2005;15:1669-73.
38. Petkovich M, Brand NJ, Krust A, Chambon P. A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature. 1987;330(6147):444- 50.
39. Giguere V, Ong ES, Segui P, Evans RM. Identification of a receptor for the morphogen retinoic acid. Nature. 1987;330(6149):624-9.
40. Brand N, Petkovich M, Krust A, Chambon P, de The H, Marchio A, et al. Identification of a second human retinoic acid receptor. Nature. 1988;332(6167):850-3.
41. Zelent A, Krust A, Petkovich M, Kastner P, Chambon P. Cloning of murine alpha and beta retinoic acid receptors and a novel receptor gamma predominantly expressed in skin. Nature. 1989;339(6227):714-7.
42. Krust A, Kastner P, Petkovich M, Zelent A, Chambon P. A third human retinoic acid receptor, hRAR-gamma. Proc Natl Acad Sci U S A. 1989;86(14):5310-4.
43. Mangelsdorf DJ, Ong ES, Dyck JA, Evans RM. Nuclear receptor that identifies a novel retinoic acid response pathway. Nature. 1990;345(6272):224-9.
44. Chambon P. A decade of molecular biology of retinoic acid receptors. FASEB J. 1996;10(9):940-54.
45. Leid M, Kastner P, Chambon P. Multiplicity generates diversity in the retinoic acid signalling pathways. Trends Biochem Sci. 1992;17(10):427-33.
46. Lemotte PK, Keidel S, Apfel CM. Phytanic acid is a retinoid X receptor ligand. Eur J Biochem. 1996;236:328-33.
47. de Urquiza AM, Liu S, Sjoberg M, Zetterstrom RH, Griffiths W, Sjovall J, Perlmann T. Docosahexaenoic acid, a ligand for the retinoid X receptor in mouse brain. Science. 2000;290:2140-4.
48. Goldstein JT, Dobrzyn A, Clagett-Dame M, Pike JW, DeLuca HF. Isolation and characterization of unsaturated fatty acids as natural ligands for the retinoid-X receptor. Arch Biochem Biophys. 2003;420:185-93.
49. Dawson MI. Synthetic retinoids and their nuclear receptors. Curr Med Chem - Anti-Cancer Agents. 2004;4:199-230.
50. Renaud JP, Moras D. Structural studies on nuclear receptors. Cell Mol Life Sci. 2000;57(12):1748-69.
51. Glass CK. Differential recognition of target genes by nuclear receptor monomers, dimers, and heterodimers. Endocr Rev. 1994;15(3):391-407.
52. Folkers GE, van der Leede BJ, van der Saag PT. The retinoic acid receptor-beta 2 contains two separate cell-specific transactivation domains, at the N-terminus and in the ligand-binding domain. Mol Endocrinol. 1993;7(4):616-27.
53. Folkers GE, van Heerde EC, van der Saag PT. Activation function 1 of retinoic acid receptor beta 2 is an acidic activator resembling VP16. J Biol Chem. 1995;270(40):23552-9.
54. Nagpal S, Friant S, Nakshatri H, Chambon P. RARs and RXRs: evidence for two autonomous transactivation functions (AF-1 and AF-2) and heterodimerization in vivo. EMBO J. 1993;12(6):2349-60.
55. Bour G, Plassat JL, Bauer A, Lalevee S, Rochette-Egly C. Vinexin beta interacts with the non-phosphorylated AF-1 domain of retinoid receptor gamma (RARgamma) and represses RARgamma-mediated transcription. J Biol Chem. 2005;280(17):17027-37.
56. Martin PJ, Lardeux V, Lefebvre P. The proliferating cell nuclear antigen regulates retinoic acid receptor transcriptional activity through direct protein-protein interaction. Nucleic Acids Res. 2005;33(13):4311-21.
57. Rochette-Egly C, Adam S, Rossignol M, Egly JM, Chambon P. Stimulation of RAR alpha activation function AF-1 through binding to the general transcription factor TFIIH and phosphorylation by CDK7. Cell. 1997;90(1):97-107.
58. Bastien J, Adam-Stitah S, Riedl T, Egly JM, Chambon P, Rochette-Egly C. TFIIH interacts with the retinoic acid receptor gamma and phosphorylates its AF-1-activating domain through cdk7. J Biol Chem. 2000;275(29):21896-904.
59. Gianni M, Tarrade A, Nigro EA, Garattini E, Rochette-Egly C. The AF-1 and AF-2 domains of RAR gamma 2 and RXR alpha cooperate for triggering the transactivation and the degradation of RAR gamma 2/RXR alpha heterodimers. J Biol Chem. 2003;278(36):34458-66
60. Bour G, Gaillard E, Bruck N, Lalevee S, Plassat JL, Busso D, et al. Cyclin H binding to the RARalpha activation function (AF)-2 domain directs phosphorylation of the AF-1 domain by cyclin-dependent kinase 7. Proc Natl Acad Sci U S A. 2005;102(46):16608-13.
61. Taneja R, Rochette-Egly C, Plassat JL, Penna L, Gaub MP, Chambon P. Phosphorylation of activation functions AF-1 and AF-2 of RAR alpha and RAR gamma is indispensable for differentiation of F9 cells upon retinoic acid and cAMP treatment. EMBO J. 1997;16(21):6452-65.
62. Rochette-Egly C, Plassat JL, Taneja R, Chambon P. The AF-1 and AF-2 activating domains of retinoic acid receptor-alpha (RARalpha) and their phosphorylation are differentially involved in parietal endodermal differentiation of F9 cells and retinoid-induced expression of target genes. Mol Endocrinol. 2000;14(9):1398-410.
63. Mascrez B, Mark M, Krezel W, Dupe V, LeMeur M, Ghyselinck NB, et al. Differential contributions of AF-1 and AF-2 activities to the developmental functions of RXR alpha. Development. 2001;128(11):2049-62.
64. Aneskievich BJ. Deletion of RAR carboxyl terminus reveals promoter- and receptor-specific AF-1 effects. Biochem Biophys Res Commun. 2001;289(5):950-6.
65. Wei LN. Retinoid receptors and their coregulators. Annu Rev Pharmacol Toxicol. 2003;43:47-72.
66. Horlein AJ, Naar AM, Heinzel T, Torchia J, Gloss B, Kurokawa R, et al. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature. 1995;377(6548):397-404.
67. Chen JD, Evans RM. A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature. 199;377(6548):454-7.
68. Heinzel T, Lavinsky RM, Mullen TM, Soderstrom M, Laherty CD, Torchia J, et al. A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression. Nature. 1997;387(6628):43-8.
69. Hu X, Lazar MA. The CoRNR motif controls the recruitment of corepressors by nuclear hormone receptors. Nature. 1999;402(6757):93-6.
70. Perissi V, Staszewski LM, McInerney EM, Kurokawa R, Krones A, Rose DW, et al. Molecular determinants of nuclear receptor-corepressor interaction. Genes Dev. 1999;13(24):3198-208.
71. Soprano DR, Qin P, Soprano KJ. Retinoic acid receptors and cancers. Annu Rev Nutr. 2004;24:201-21.
72. Perez A, Kastner P, Sethi S, Lutz Y, Reibel C, Chambon P. PML-RAR homodimers: distinct DNA binding proteins and heteromeric interactions with RXR. EMBO J. 1993;12:3171-82.
73. Lin RJ, Evans RM. Acquisition of oncogenic potential by RAR chimeras in acute promyelocytic leukemia through formation of homodimers. Mol Cell. 2000;5:821-30.
74. Redner BA, Chen JD, Rush EA, Li H, Pollock SL. The t(5;17) acute promyelocytic leukemia fusion protein NPM-RAR interacts with co-repressor and co-activator proteins and exhibits both positive and negative transcriptional properties. Blood. 2000;95:2683-90.
75. Ruthardt M, Testa U, Nervi C, Ferrucci PF, Grignani F, Puccetti E, Grignani F, Peschle C, Pelicci PG. Opposite effects of the acute promyelocytic leukemia PML-retinoic acid receptor alpha (RAR alpha) and PLZF-RAR alpha fusion proteins on retinoic acid signalling. Mol Cell Biol. 1997;17:4859-69.
76. Maurer AB, Wichmann C, Gross A, Kunkel H, Heinzel T, Ruthardt M, Groner B, Grez M. The Stat5-RARalpha fusion protein represses transcription and differentiation through interactions with a corepressor complex. Blood. 2002;99:2647-52.
77. Gupta V, Tabak D, Keating A. Acute promyelocytic leukemia: a case-based review. Hematology. 2003;8:105-13.
78. Sirulnik LA, Stone RM. Acute promyelocytic leukemia: current strategies for the treatment of newly diagnosed disease. Clin Adv Hematol Oncol. 2005;3:391-7.
79. Sanz MA, Fenaux P, Lo Coco F; European APL Group of Experts. Arsenic trioxide in the treatment of acute promyelocytic leukemia. A review of current evidence. Haematologica. 2005;90:1231-5.
80. Rojewski MT, Korper S, Schrezenmeier H. Arsenic trioxide therapy in acute promyelocytic leukemia and beyond: from bench to bedside. Leuk Lymphoma. 2004;45:2387-401.
81. Lin RJ, Nagy L, Inoue S, Shao W, Miller WH, Evans RM. Role of the histone deacetylase complex in acute promyelocytic leukaemia. Nature. 1998;391:811-4.
82. Fazi F, Travaglini L, Carotti D, Palitti F, Diverio D, Alcalay M, McNamara S, Miller WH, Lo Coco F, Pelicci PG, Nervi C. Retinoic acid targets DNA-methyltransferases and histone deacetylases during APL blast differentiation in vitro and in vivo. Oncogene. 2005;24:1820-30.
83. Geisen C, Denk C, Gremm B, Baust C, Karger A, Bollag W. Schwarz E. High-level expression of the retinoic acid receptor beta gene in normal cells of the uterine cervix is regulated by the retinoic acid receptor alpha and is abnormally down-regulated in cervical carcinoma cells. Cancer Res. 1997;57:1460-7.
84. McGregor F, Wagner E, Felix D, Soutar D, Parkinson K, Harrison PR. Inappropriate retinoic acid receptor-beta expression in oral dysplasias: correlation with acquisition of the immortal phenotype. Cancer Res. 1997;57:3886-9.
85. Picard E, Seguin C, Momhoven N, Rochette-Egly C, Siat J, Borrelly J, Martinet Y, Martinet N, Vignaud JM. Expression of retinoid receptor genes and proteins in non-small-cell lung cancer. J Natl Cancer Inst. 1999;91:1059-66.
86. Qiu H, Zhang W, El-Naggar AK, Lippman SM, Lin P, Lotan R, Xu XC. Loss of retinoic acid receptor-beta expression is an early event during esophageal carcinogenesis. Am J Pathol. 1999;155:1519-23.
87. Swisshelm K, Ryan K, Lee X, Tsou HC, Peacocke M, Sager R. Down-regulation of retinoic acid receptor beta in mammary carcinoma cell lines and its upregulation in senescing normal mammary epithelial cells. Cell Growth Differ. 1994;5:133-41.
88. Widschwendter M, Berger J, Daxenbichler G, Muller-Holzner E, Widschwendter A, Mayr A, Marth C, Zaiment AG. Loss of retinoic acid receptor expression in breast cancer and morphologically normal adjacent tissues but not in the normal breast tissue distant from the cancer. Cancer Res. 1997;57:4156-61.
89. Wu S, Zhang D, Zhang ZP, Soprano DR, Soprano KJ. Critical role of both retinoid nuclear receptors and retinoid-X-receptors in mediating growth inhibition of ovarian cancer cells by all-trans retinoic acid. Oncogene. 1999;17:2839-49.
90. Xu XC, Ro JY, Lee JS, Shin DM, Hong WK, Lotan R. Differential expression of nuclear retinoid receptors in normal, premaligant, and malignant head and neck tissues. Cancer Res. 1994;54:3580-7.
91. Xu XC, Sneige N, Liu X, Nandagiri R, Lee JJ, Lukmanji F, Hortobagyi G, Lippmann SM, Dhingra K, Lotan R. Progressive decrease in nuclear retinoic acid receptor beta messenger RNA level during breast carcinogenesis. Cancer Res. 1997;57:4992-6.
92. Zhang XK, Liu Y, Lee MO, Pfahl M. A specific defect in the retinoic acid response associated with human lung cancer cell lines. Cancer Res. 1994;54:5663-9.
93. Hayashi K, Yokozaki H, Naka K, Yasui W, Lotan R, Tahara E. Overexpression of retinoic acid receptor beta induces growth arrest and apoptosis in oral cancer cell lines. Jpn J Cancer Res. 2001;92:42-50.
94. Li M, Song S, Lippman SM, Zhang XK, Liu X, Lotan R, Xu XC. Induction of retinoic acid receptor-beta suppresses cyclooxygenase-2 expression in esophageal cancer cells. Oncogene. 2002;21:411-8.
95. Li Y, Dawson MI, Agadir A, Lee MO, Jong L, Hobbs PD, Zhang XK. Regulation of RAR beta expression by RAR- and RXR-selective retinoids in human lung cancer cell lines: effect on growth inhibition and apoptosis induction. Int J Cancer. 1998;75:88-95.
96. Seewaldt VL, Johnson BS, Parker MB, Collins SJ, Swisshelm K. Expression of retinoic acid receptor beta mediates retinoic acid-induced growth arrest and apoptosis in breast cancer cells. Cell Growth Differ. 1995;6:1077-88.
97. Xu XC, Liu X, Tahara E, Lippman SM, Lotan R. Expression and up-regulation of retinoic acid receptor-beta is associated with retinoid sensitivity and colony formation in esophageal cancer cell lines. Cancer Res. 1999;59:2477-83.
98. Germain P, Iyer J, Zechel C, Gronemeyer H. Coregulator recruitment and the mechanism of retinoic acid receptor synergy. Nature. 2002;415:187-92.
99. Lin F, Xiao D, Kolluri SK, Zhang X. Unique antiactivator protein-1 activity of retinoic acid receptor beta. Cancer Res. 2000;60:3271-80.
100. Arce JD, Soto U, van Riggelen J, Schwarz E, zur Hausen H, Rosl F. Ectopic expression on nonliganded retinoic acid receptorβ abrogates AP-1 activity by selective degradation of c-jun in cervical carcinoma cells. J Biol Chem. 2004;279:45408-16.
101. Lin B, Chen G, Xiao D, Lolluri SK, Cao X, Su H, Zhang X. Orphan receptor COUP-TF is required for induction of retinoic acid receptor, growth inhibition and apoptosis by retinoic acid in cancer cells. Mol Cell Biol. 2000;20:957-70.
102. Wu Q, Li Y, Liu R, Agadir A, Lee MO, Liu Y, Zhang X. Modulation of retinoic acid sensitivity in lung cancer cells through dynamic balance of orphan receptors nurr77 and COUP TF and their heterodimerization. EMBO J. 1997;16:1656-69.
103. Arapshian A, Kuppumbatti YS, Mira-y-Lopez R. Methylation of conserved CpG sites neighboring the beta retinoic acid response element may mediate retinoic acid receptor beta gene silencing in MCF-7 breast cancer cells. Oncogene. 2000;19:4066-70.
104. Bovenzi V, Le NL, Cote S, Sinnett D, Momparler LF, Momparler RL. DNA methylation of retinoic acid receptor beta in breast cancer and possible therapeutic role of 5-aza-2′deoxycytidine. Anticancer Drug. 1999;10:471-6.
105. Cote S, Sinnett D, Momparler RL. Demethylation by 5-aza- 2′deoxycytidine of specific 5-methylcytosine sites in the promoter region of the retinoic acid receptor beta gene in human colon carcinoma cells. Anticancer Drugs. 1998;9:743-50.
106. Hayashi K, Yokozaki H, Goodison S, Oue N, Suzuki T, Lotan R, Yasui W, Tahara E. Inactivation of retinoic acid receptor beta by promoter CpG hypermethylation in gastric cancer. Differentiation. 2001;69:13-21.
107. Nakayama T, Watanabe M, Yamanaka M, Hirokawa Y, Suzuki H, Ito H, Yatani R, Shiraishi T. The role of epigenetic modifications in retinoic acid receptor beta2 gene expression in human prostate cancers. Lab Invest. 2001;81:1049-57.
108. Oshita F, Sekiyama A, Suzuki R, Ikehara M, Yamada K, Saito H, Noda K, Miyagi Y. Detection of occult tumor cells in peripheral blood from patients with small cell lung cancer by promoter methylation and silencing of the retinoic acid receptor-beta. Oncol Rep. 2003;10:105-8.
109. Widschwendter M, Berger J, Hermann M, Muller HM, Amberger A, Zeschnigk M, Widschwendter A, Abendstein B, Zeimet AG, Daxenbichler G, Marth C. Methylation and silencing of the retinoic acid receptor-beta2 gene in breast cancer. J Natl Cancer Inst. 2000;92:826-32.
110. Zochbauer-Muller S, Fong KM, Virmani AK, Geradts J, Gazdar AF, Minna JD. Aberrant promoter methylation of multiple genes in non-small cell lung cancers. Cancer Res. 2001;61:249-55.
111. Cote S, Momparler RL. Activation of the retinoic acid receptor beta gene by 5-aza-2′-deoxyctytidine in human DLD-1 colon carcinoma cells. Anticancer Drugs. 1997;8:56-61.
112. Sirchia SM, Ren M, Pili R, Siron E, Somenzi G, Ghidoni R, Toma S, Nicolo G, Sacchi N. Endogenous reactivation of the RARβ2 tumor suppressor gene epigenetically silenced in breast cancer. Cancer Res. 2002;62:2455-61.
113. Bovenzi V, Momparler RL. Antineoplastic action of 5-aza- 2′deoxycytidine and histone deacetylase inhibitor and their effect on the expression of retinoic acid receptor beta and estrogen receptor alpha genes in breast carcinoma cells. Cancer Chemother Pharmacol. 2001;48:71-6.
114. Pfahl M. Nuclear receptor/AP1 interaction. Endocr Rev. 1993;14:651-8.
115. Kamei Y, Xu L, Heinzel T, Torchia J, Kurokawa R, Gloss B, Lin SC, Heyman RA, Rose DW, Glass CK, Rosenfeld MG. A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell. 1996;85:403-14.
116. Caelles C, Gonzalez-Sancho JM, Munoz A. Nuclear hormone receptor antagonism with AP-1 by inhibition of the JNK pathway. Genes Dev. 1997;11:3351-64.
117. Zhou XF, Shen XQ, Shemshedini L. Ligand-activated retinoic acid receptor inhibits AP-1 transactivation by disrupting c-jun/c-fos dimerization. Mol Endocrinol. 1999;13:281-9.
118. Ramirez CJ, Haberbusch JM, Soprano DR, Soprano KJ. Retinoic acid induced repression of AP-1 activity is mediated by protein phosphatase 2A in ovarian carcinoma cells. J Cell Biochem. 2005;96:170-82.
119. Fanjul A, Dawson MI, Hobbs PD, Jong L, Camerson JF, Harley E, Graupner G, Lu XP, Pfahl M. A new class of retinoids with selective inhibition of AP-1 inhibits proliferation. Nature. 1994;372:107-11.
120. Liu Y, Lee MO, Wang HG, Li Y, Hashimoto Y, Klaus M, Reed JC, Zhang X. Retinoic acid receptor beta mediates the growth-inhibitory effect of retinoic acid by promoting apoptosis in human breast cancer cells. Mol Cell Biol. 1996;16:1138-49.
121. Pfahl M, Piedrafita FJ. Retinoid targets for apoptosis induction. Oncogene. 2003;22:9058-62.
122. O'Connell MJ, Chua R, Hoyos B, Buck J, Chen Y, Derguini F, Hammerling U. Retro-retinoids in regulated cell growth and death. J Exp Med. 1996;184:549-55.
123. Imam A, Hoyos B, Swenson C, Levi E, Chua R, Viriya E, Hammerling U. Retinoids as ligands and coactivators of protein kinase C alpha. FASEB J. 2001;15:28-30.
124. Hoyos B, Imam A, Korichneva I, Levi E, Chua R, Hammerling U. Activation of c-Raf kinase by ultraviolet light. Regulation by retinoids. J Biol Chem. 2002;277:23949-57.
125. Hoyos B, Jiang S, Hammerling U. Location and functional significance of retinol-binding sites on the serine/threonine kinase, c-Raf. J Biol Chem. 2005;280:6872-8.
126. Delia D, Aiello A, Lombardi L, Pelicci PG, Grignani F, Grignani F, Formelli F, Menard S, Costa A, Veronesi U, Pierotti MA. N-(4-hydroxyphenyl) retinamide induces apoptosis of maligant hemopoietic cell lines including those unresponsive to retinoic acid. Cancer Res. 1993;53:6036-41.
127. Holmes WF, Soprano DR, Soprano KJ. Comparison of the mechanism of induction of apoptosis in ovarian carcinoma cells by the conformationally restricted synthetic retinoids CD437 and 4-HPR. J Cell Biochem. 2003;89:262-78.
128. Hsieh TC, Wu JM. Effects of fenretinide (4-HPR) on prostate LNCaP cell growth, apoptosis, and prostate-specific gene expression. Prostate. 1997;33:97-104.
129. Kalemkerian GP, Slusher R, Ramalingam S, Gadgeel S, Mabry M. Growth inhibition and induction of apoptosis by fenretinide in small-cell lung cancer cell lines. J Natl Cancer Inst. 1995;87:1674-80.
130. Ponzoni M, Bocca P, Chiesa V, Decensi A, Pistoia V, Raffaghello L, Rozzo C, Montaldo PG. Differential effects of N-(4-hydroxyphenyl)retinamide and retinoic acid on neuroblastoma cells: apoptosis versus differentiation. Cancer Res. 1995;55:853-61.
131. Wang TT, Phang JM. Effect of N-(4-hydroxyphenyl) retinamide on apoptosis in human breast cancer cells. Cancer Lett. 1996;107:65-71.
132. Fanjul AN, Delia D, Pierotti MA, Rideout D, Yu JQ, Pfahl M. 4-hydroxyphenyl retinamide is a highly selective activator of retinoid receptors. J Biol Chem. 1996;271:22441-6.
133. Wu JM, DiPietrantonio AM, Hsieh TC. Mechanism of fenretinide (4-HPR)-induced cell death. Apoptosis. 2001;6:377-88.
134. Adachi H, Preston G, Harvat B, Dawson MI, Jetten AM. Inhibition of cell proliferation and induction of apoptosis by the retinoid AHPN in human lung carcinoma cells. Am J Respir Cell Mol Biol. 1998;18:323-33.
135. Bayon Y, Ortiz MA, Lopez-Hernandez FJ, Gao F, Karin M, Pfahl M, Piedrafita FJ. Inhibition of IkappaB kinase by a new class of retinoid-related anticancer agents that induce apoptosis. Mol Cell Biol. 2003;23:1061-74.
136. Costa SL, Paillaud E, Eages C, Rochette-Egly C, Plassat JL, Jouault H, Perzelova A, Tardy M. Effects of a novel synthetic retinoid on malignant glioma in vitro: inhibition of cell proliferation, induction of apoptosis and differentiation. Eur J Cancer. 2001;37:520-30.
137. Hail N, Lotan R. Synthetic retinoid CD437 promotes rapid apoptosis in malignant human epidermal keratinocytes and G1 arrest in their normal counterparts. J Cell Physiol. 2001;186:24-34.
138. Lu XP, Fanjul A, Picard N, Pfahl M, Rungta D, Nared-Hood K, Carter B, Piedrafita J, Tang S, Fabbrizio E, Pfahl M. Novel retinoid-related molecules as apoptosis inducers and effective inhibitors of human lung cancer cells in vivo. Nat Med. 1997;3:686-90.
139. Marchetti JB, Lefebvre O, Schraen-Maschke S, Mereau-Richard C, Formstecher P. The novel retinoid AHPN/CD437 induces a rapid but incomplete apoptotic response in human myeloma cells. Biochem Biophys Acta. 2003;1593:277-82.
140. Oridate N, Higuchi M, Suzuki S, Shroot B, Hong WK, Lotan R. Rapid induction of apoptosis in human C33A cervical carcinoma cells by the synthetic retinoid 6-[3-(1-adamantyl)hydroxyphenyl]-2-naphtalene carboxylic acid (CD437). Int J Cancer. 1997;70:484-7.
141. Sun SY, Yue P, Chen X, Hong WK, Lotan R. The synthetic retinoid CD437 induces apoptosis in human lung cancer cells while sparing normal human lung epithelial cells. Cancer Res. 2002;62:2430-6.
142. Holmes WF, Dawson MI, Soprano DR, Soprano KJ. Induction of apoptosis in ovarian carcinoma cells AHPN/CD437 is mediated by retinoic acid receptors. J Cell Physiol. 2000;185:61-7.
143. Holmes WF, Soprano DR, Soprano KJ. Elucidation of molecular events mediating induction of apoptosis by synthetic retinoids using a CD437-resistant ovarian carcinoma cell line. J Biol Chem. 2002;277:45408-19.
144. Holmes WF, Soprano DR, Soprano KJ. Early events in the induction of apoptosis in ovarian carcinoma cells by CD437: activation of the p38 MAP kinase signal pathway. Oncogene. 2003;22:6377-86.
145. Hsu CA, Rishi AK, Su-Li X, Gerald TM, Dawson MI, Schiffer C, Reichert U, Shroot B, Poirer GC, Fontana JA. Retinoid induced apoptosis in leukemia cells through a retinoic acid nuclear receptor-independent pathway. Blood. 1997;89:4470-9.
146. Li Y, Lin B, Agadir A, Liu R, Dawson MI, Reed JC, Fontana JA, Bost F, Hobbs PD, Zheng Y, Chen GQ, Shroot B, Mercola D, Zhang XK. Molecular determinant of AHPN (CD437)-induced growth arrest and apoptosis in human lung cancer cell lines. Mol Cell Biol. 1998;19:4719-31.
147. Sun SY, Yue P, Lotan R. Implication of multiple mechanisms in apoptosis induced by the synthetic retinoid CD437 in human prostate carcinoma cells. Oncogene. 2000;19:4513-22.
148. Sun SY, Yue P, Wu GC, El-Deiry WS, Shroot B, Hong WK, Lotan R. Mechanism of apoptosis induced by the synthetic retinoid CD437 in human non-small cell lung carcinoma cells. Oncogene. 1999;18:2357-65.
149. Zhao Z, Demary K, Wong L, Vaziri C, McKenzie AB, Eberlein TJ, Spanjaard RA. Retinoic acid receptor-independent mechanism of apoptosis of melanoma cells by the retinoid CD437 (AHPN). Cell Death Differ. 2001;8:878-86.
150. Benbrook DM. Refining retinoids with heteroatoms. Mini Rev Med Chem. 2002;2:277-83.
151. Benbrook DM, Kamelle SA, Guruswamy SB, Lightfoot SA, Rutledge TL, Gould NS, Hannafon BN, Dunn ST, Berlin KD. Flexible heteroarotinoids (Flex-Hets) exhibit improved therapeutic ratios as anti-cancer agents over retinoic acid receptor agonists. Investig New Drugs. 2005;23:417-28.
152. Chun K-H, Benbrook DM, Berlin KD, Hong WK, Lotan R. The synthetic heteroarotinoid SHetA2 induces apoptosis in squamous carcinoma cells through a receptor-independent and mitochondria-dependent pathway. Cancer Res. 2003;63:3826-32.
153. Liu S, Brown CW, Berlin KD, Dhar A, Guruswamy S, Brown D, Gardner GJ, Birrer MJ, Benbrook DM. Synthesis of flexible sulfur-containing heteroarotinoids that induce apoptosis and reactive oxygen species with discrimination between malignant and benign cells. J Med Chem. 2004;47:999-1007.
154. Farol LT, Hymes KB. Bexarotene: a clinical review. Expert Rev Anticancer Ther. 2004;4:180-8.
155. Rigas JR, Dragnev KH. Emerging role of rexinoids in non-small cell lung cancer: focus on bexarotene. Oncologist. 2005;10:22-33.