Белки CRABP – родственники или однофамильцы?

Ретиноевая кислота (РК) – наиболее активный метаболит витамина А (ретинола), регулирующий широкий спектр физиологических процессов в организме, в том числе эмбриональное развитие, формирование иммунного ответа, гемопоэз, метаболизм глюкозы и липидов и др. РК участвует в регуляции важнейших аспектов жизнедеятельности клеток, включая дифференцировку, пролиферацию и программируемую клеточную гибель. Обзор посвящен сравнению 2 высокогомологичных представителей семейства внутриклеточных липидсвязывающих белков CRABP1 и CRABP2, основная и единственно установленная на сегодняшний день функция которых – внутриклеточное связывание РК. Однако значение данного связывания, по-видимому, различно. Связывание СRABP2 с РК приводит к активации ядерных рецепторов (RAR / RXR), являющихся транскрипционными факторами, и последующей стимуляции экспрессии целого ряда ретиноид-респонсивных генов. Значение связывания CRABP1 с РК менее понятно. Есть свидетельства сходного действия белков CRABP1 и CRABP2 в отношении усиления эффекта РК, однако большая часть данных указывает на противоположную роль CRABP1 – снижение внутриклеточной концентрации и / или уменьшение биодоступности РК за счет усиления ее метаболизма или секвестрирования в цитоплазме. Результаты последних исследований указывают на то, что у белков СRABP могут быть функции, не связанные с проведением сигнала от РК. Также противоречивы данные о роли этих белков в канцерогенезе и опухолевой прогрессии. В обзоре рассматриваются функции РК и молекулярные механизмы, опосредующие ее активность, включая различные аспекты функционирования рецепторов РК, приводится сравнительный анализ структурно-функциональных характеристик белков CRABP и рассматриваются возможные механизмы их внутриклеточной активности, как связанные с РК, так и независимые от ретиноевого сигналинга. Особое внимание уделено анализу данных о связи белков CRABP с канцерогенезом и их участию в опухолевой прогрессии, в том числе указывающих как на опухоль-супрессорную функцию, так и на протуморогенную активность.

ретиноевая кислота, рецепторы ретиноевой кислоты, ретиноид-респонсивные гены, белок CRABP1, белок CRABP2, опухолевая прогрессия

1. Gutierrez-Gonzalez L.H., Ludwig C., Hohoff C. et al. Solution structure and backbone dynamics of human epidermal-type fatty acid-binding protein (E-FABP). Biochem J 2002;364(Pt 3):725–37.

2. Kleywegt G.J., Bergfors T., Senn H. et al. Crystal structures of cellular retinoic acid binding proteins I and II in complex with alltrans-retinoic acid and a synthetic retinoid. Structure 1994;2(12):1241–58.

3. Veerkamp J.H., Maatman R.G. Cytoplasmic fatty acid-binding proteins: their structure and genes. Prog Lipid Res 1995;34(1):17–52.

4. Thaller C., Eichele G. Identification and spatial distribution of retinoids in the developing chick limb bud. Nature 1987;327(6123):625–628.

5. S pinella M.J., Kerley J.S., White K.A. et al. Retinoid target gene activation during induced tumor cell differentiation: human embryonal carcinoma as a model. J Nutr 2003;133(1):273S–6S.

6. Ma den M. Role and distribution of retinoic acid during CNS development. Int Rev Cytol 2001;209:1–77.

7. Mad en M. Retinoids in lung development and regeneration. Curr Top Dev Biol 2004;61:153–89.

8. Thal ler C., Eichele G. Retinoid signaling in vertebrate limb development. Ann NY Acad Sci 1996;785:1–11.

9. Colli ns S.J. The role of retinoids and retinoic acid receptors in normal hematopoiesis. Leukemia 2002;16(10): 1896–905.

10. Morik awa K., Nonaka M. All-transretinoic acid accelerates the differentiation of human B lymphocytes maturing into plasma cells. Int Immunopharmacol 2005;5(13–14):1830–8.

11. Iwata M . Retinoic acid production by intestinal dendritic cells and its role in T-cell trafficking. Semin Immunol 2009;21(1):8–13.

12. Rhinn M. , Dolle P. Retinoic acid signalling during development. Development 2012;139(5):843–58.

13. Theodosio u M., Laudet V., Schubert M. From carrot to clinic: an overview of the retinoic acid signaling pathway. Cell Mol Life Sci 2010;67(9):1423–45.

14. Huang Y., Boskovic G., Niles R.M. Retinoic acid-induced AP-1 transcriptional activity regulates B16 mouse melanoma growth inhibition and differentiation. J Cell Physiol 2003;194(2):162–70.

15. Breitman T. R., Selonick S.E., Collins S.J. Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid. Proc Natl Acad Sci USA 1980;77(5):2936–40.

16. Wu S., Donig an A., Platsoucas C.D. et al. All-trans-retinoic acid blocks cell cycle progression of human ovarian adenocarcinoma cells at late G1. Exp Cell Res 1997;232(2):277–286.

17. Singh B., Mur phy R.F., Ding X.Z. et al. On the role of transforming growth factorbeta in the growth inhibitory effects of retinoic acid in human pancreatic cancer cells. Mol Cancer 2007;6:82.

18. Battle T.E., Roberson M.S., Zhang T. et al. Retinoic acid-induced blr1 expression requires RARalpha, RXR, and MAPK activation and uses ERK2 but not JNK/ SAPK to accelerate cell differentiation. Eur J Cell Biol 2001;80(1): 59–67.

19. Strickland S., Mahdavi V. The induction of differentiation in teratocarcinoma stem cells by retinoic acid. Cell 1978;15(2): 393–403.

20. Altucci L., Ros sin A., Raffelsberger W. et al. Retinoic acid-induced apoptosis in leukemia cells is mediated by paracrine action of tumor-selective death ligand TRAIL. Nat Med 2001;7(6):680–6.

21. Elstner E., Mull er C., Koshizuka K. et al. Ligands for peroxisome proliferator-activated

22. receptorgamma and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice. Proc Natl Acad Sci USA 1998;95(15): 8806–11.

23. Toma S., Isnardi L., Riccardi L. et al. Induction of apoptosis in MCF-7 breast carcinoma cell line by RAR and RXR selective retinoids. Anticancer Res 1998;18(2A):935–42.

24. Mangiarotti R., Da nova M., Alberici R., Pellicciari C. All-trans retinoic acid (ATRA)-induced apoptosis is preceded by G1 arrest in human MCF-7 breast cancer cells. Br J Cancer 1998;77(2):186–91.

25. Luo P., Lin M., Lin M. et al. Function of retinoid acid receptor alpha and p21 in all-trans-retinoic acid-induced acute T-lymphoblastic leukemia apoptosis. Leuk Lymphoma 2009;50(7):1183–9.

26. Kini A.R., Peterson L.A., Tallman M.S. et al. Angiogenesis in acute promyelocytic leukemia: induction by vascular endothelial growth factor and inhibition by all-trans retinoic acid. Blood 2001;97(12):3919–24.

27. Kim M.S., Kim Y.K., E un H.C. et al. Alltrans retinoic acid antagonizes UV-induced VEGF production and angiogenesis via the inhibition of ERK activation in human skin keratinocytes. J Invest Dermatol 2006;126(12):2697–706.

28. Pfahl M., Piedrafita F .J. Retinoid targets for apoptosis induction. Oncogene 2003;22(56):9058–62.

29. Sadikoglou E., Magoulas G., Theodoropoulou C. et al. Effect of conjugates of all-trans-retinoic acid and shorter polyene chain analogues with amino acids on prostate cancer cell growth. Eur J Med Chem 2009;44(8):3175–87.

30. Lee J.H., Yoon J.H., Yu S.J. et al. Retinoic acid and its binding protein modulate apoptotic signals in hypoxic hepatocellular carcinoma cells. Cancer Lett 2010;295(2):229–35.

31. Donato L.J., Noy N. Suppr ession 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(18):8193–9.

32. Hoang T.C., Bui T.K., Tagu chi T. et al. All-trans retinoic acid inhibits KIT activity and induces apoptosis in gastrointestinal stromal tumor GIST-T1 cell line by affecting on the expression of survivin and Bax protein. J Exp Clin Cancer Res 2010;29:165.

33. Khuri F.R., Lippman S.M., Spitz M.R. et al. Molecular epidemiology and retinoid chemoprevention of head and neck cancer. J Natl Cancer Inst 1997;89(3):199–211.

34. Zuccari G., Carosio R., Fin i A. et al. Modified polyvinylalcohol for encapsulation of all-trans-retinoic acid in polymeric micelles. J Control Release 2005;103(2):369–80.

35. Caselli E., Galvan M., Santo ni F. et al. Retinoic acid analogues inhibit human herpesvirus 8 replication. Antivir Ther 2008;13(2):199–209.

36. Kang S., Duell E.A., Fisher G .J. et al. Application of retinol to human skin in vivo induces epidermal hyperplasia and cellular retinoid binding proteins characteristic of retinoic acid but without measurable retinoic acid levels or irritation. J Invest Dermatol 1995;105(4):549–56.

37. Verma A.K., Conrad E.A., Boutw ell R.K. Differential effects of retinoic acid and 7,8-benzoflavone on the induction of mouse skin tumors by the complete carcinogenesis process and by the initiation-promotion regimen. Cancer Res 1982;42(9): 3519–25.

38. Zouboulis C.C. Retinoids–which dermatological indications will benefit in the near future? Skin Pharmacol Appl Skin Physiol 2001;14(5):303–15.

39. Henion P.D., Weston J.A. Retinoi c acid selectively promotes the survival and proliferation of neurogenic precursors in cultured neural crest cell populations. Dev Biol 1994;161(1):243–50.

40. Jacobs S., Lie D.C., DeCicco K.L. et al. Retinoic acid is required early during adult neurogenesis in the dentate gyrus. Proc Natl Acad Sci USA 2006; 103(10):3902–7.

41. Plum L.A., Parada L.F., Tsoulfas P . et al. Retinoic acid combined with neurotrophin-3 enhances the survival and neurite outgrowth of embryonic sympathetic neurons. Exp Biol Med 2001;226(8):766–75.

42. Rodriguez-Tebar A., Rohrer H. Retin oic acid induces NGF-dependent survival response and high-affinity NGF receptors in immature chick sympathetic neurons. Development 1991;112(3):813–20.

43. Heyman R.A., Mangelsdorf D.J., Dyck J.A. et al. 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell 1992;68(2):397–406.

44. Duong V., Rochette-Egly C. The molecular physiology of nuclear retinoic acid receptors. From health to disease. Biochim Biophys Acta 2011;1812(8):1023–31.

45. de The H., Vivanco-Ruiz M.M., Tiollais P. et al. Identification of a retinoic acid responsive element in the retinoic acid receptor beta gene. Nature 1990;343(6254):177–80.

46. Perissi V., Jepsen K., Glass C.K., Rose nfeld M.G. Deconstructing repression: evolving models of co-repressor action. Nat Rev Genet 2010;11(2):109–23.

47. le Maire A., Teyssier C., Erb C. et al. A unique secondary-structure switch controls constitutive gene repression by retinoic acid receptor. Nat Struct Mol Biol 2010;17(7): 801–7.

48. Shaw N., Elholm M., Noy N. Retinoic acid is a high affinity selective ligand for the peroxisome proliferator-activated receptor beta/delta. J Biol Chem 2003;278(43): 41589–92.

49. Schug T.T., Berry D.C., Shaw N.S. et al. O pposing effects of retinoic acid on cell growth result from alternate activation of two different nuclear receptors. Cell 2007;129(4): 723–33.

50. Dong D., Ruuska S.E., Levinthal D.J. et al. Distinct roles for cellular retinoic acid-binding proteins I and II in regulating signaling by retinoic acid. J Biol Chem 1999;274(34):23695–8.

51. Budhu A.S., Noy N. Direct channeling of reti noic acid between cellular retinoic acidbinding protein II and retinoic acid receptor sensitizes mammary carcinoma cells to retinoic acid-induced growth arrest. Mol Cell Biol 2002;22(8):2632–41.

52. Sessler R.J., Noy N. A ligand-activated nucle ar localization signal in cellular retinoic acid binding protein-II. Mol Cell 2005;18(3):343–53.

53. Manor D., Shmidt E.N., Budhu A. et al. Mammary carcinoma suppression by cellular retinoic acid binding protein-II. Cancer Res 2003;63(15):4426–33.

54. Tan N.S., Shaw N.S., Vinckenbosch N. et al. Sel ective cooperation between fatty acid binding proteins and peroxisome proliferator-activated receptors in regulating transcription. Mol Cell Biol 2002;22(14): 5114–27.

55. Sussman F., de Lera A.R. Ligand recognition by R AR and RXR receptors: binding and selectivity. J Med Chem 2005;48(20):6212–9.

56. Afonja O., Raaka B.M., Huang A. et al. RAR agonis ts stimulate SOX9 gene expression in breast cancer cell lines: evidence for a role in retinoid-mediated growth inhibition. Oncogene 2002;21(51):7850–60.

57. Afonja O., Juste D., Das S. et al. Induction of PD CD4 tumor suppressor gene expression by RAR agonists, antiestrogen and HER-2/neu antagonist in breast cancer cells. Evidence for a role in apoptosis. Oncogene 2004;23(49): 8135–45.

58. Zacheis D., Dhar A., Lu S. et al. Heteroarotinoids inhibit head and neck cancer cell lines in vitro and in vivo through both RAR and RXR retinoic acid receptors. J Med Chem 1999;42(21):4434–45.

59. Soprano D.R., Qin P., Soprano K.J. Retinoic acid rec eptors and cancers. Annu Rev Nutr 2004;24:201–21.

60. Donato L.J., Suh J.H., Noy N. Suppression of mammary carcinoma cell growth by retinoic acid: the cell cycle control gene Btg2 is a direct target for retinoic acid receptor signaling. Cancer Res 2007;67(2):609–15.

61. Noy N. Between death and survival: retinoic acid in re gulation of apoptosis. Annu Rev Nutr 2010;30:201–17.

62. Di-Poi N., Michalik L., Tan N.S. et al. The anti-apopto tic role of PPARbeta contributes to efficient skin wound healing. J Steroid Biochem Mol Biol 2003;85(2–5): 257–65.

63. Di-Poi N., Tan N.S., Michalik L. et al. Antiapoptotic rol e of PPARbeta in keratinocytes via transcriptional control of the Akt1 signaling pathway. Mol Cell 2002;10(4):721–33.

64. Aggarwal B.B., Sethi G., Ahn K.S. et al. Targeting signal transducer and activator of transcription-3 for prevention and therapy of cancer: modern target but ancient solution. Ann NY Acad Sci 2006;1091:151–69.

65. Montagner A., Delgado M.B., TallichetBlanc C. et al. Src i s activated by the nuclear receptor peroxisome proliferator-activated receptor beta/delta in ultraviolet radiationinduced skin cancer. EMBO Mol Med 2014;6(1):80–98.

66. Schug T.T., Berry D.C., Toshkov I.A. et al. Overcoming retin oic acid-resistance of mammary carcinomas by diverting retinoic acid from PPARbeta/delta to RAR. Proc Natl Acad Sci USA 2008;105(21):7546–51.

67. Morgan E., Kannan-Thulasiraman P., Noy N. Involvement of Fatt y Acid Binding Protein 5 and PPARbeta/delta in Prostate Cancer Cell Growth. PPAR Res 2010; 2010.

68. Levi L., Lobo G., Doud M.K. et al. Genetic ablation of the fa tty acid-binding protein FABP5 suppresses HER2-induced mammary tumorigenesis. Cancer Res 2013;73(15):4770–80.

69. White J.A., Guo Y.D., Baetz K. et al. Identification of the re tinoic acid-inducible all-trans-retinoic acid 4-hydroxylase. J Biol Chem 1996;271(47):29922–7.

70. Liu H.X., Ly I., Hu Y., Wan Y.J. Retinoic acid regulates cell c ycle genes and accelerates normal mouse liver regeneration. Biochem Pharmacol 2014;91(2):256–65.

71. Chaudhuri B.N., Kleywegt G.J., BroutinL'Hermite I. et al. Struc tures of cellular retinoic acid binding proteins I and II in complex with synthetic retinoids. Acta Crystallogr D Biol Crystallogr 1999;55(Pt 11):1850–7.

72. Li X.H., Ong D.E. Cellular retinoic acidbinding protein II gene expression is directly induced by estrogen, but not retinoic acid, in rat uterus. J Biol Chem 2003;278(37):35819–25.

73. Lu M., Mira-y-Lopez R., Nakajo S. et al. Expression of estrogen re ceptor alpha, retinoic acid receptor alpha and cellular retinoic acid binding protein II genes is coordinately regulated in human breast cancer cells. Oncogene 2005;24(27):4362–9.

74. Maden M. Retinoid signalling in the development of the central nerv ous system. Nat Rev Neurosci 2002;3(11):843–53.

75. Bucco R.A., Zheng W.L., Davis J.T. et al. Cellular retinoic acid-bin ding protein(II) presence in rat uterine epithelial cells correlates with their synthesis of retinoic acid. Biochemistry 1997;36(13):4009–14.

76. Wardlaw S.A., Bucco R.A., Zheng W.L., Ong D.E. Variable expression of cellular retinol- and cellular retinoic acid-binding proteins in the rat uterus and ovary during the estrous cycle. Biol Reprod 1997;56(1):125–32.

77. Zheng W.L., Ong D.E. Spatial and temporal patterns of expression of ce llular retinol-binding protein and cellular retinoic acid-binding proteins in rat uterus during early pregnancy. Biol Reprod 1998;58(4):963–70.

78. Yamamoto M., Drager U.C., Ong D.E., McCaffery P. Retinoid-binding prote ins in the cerebellum and choroid plexus and their relationship to regionalized retinoic acid synthesis and degradation. Eur J Biochem 1998;257(2):344–50.

79. Kitareewan S., Pitha-Rowe I., Sekula D. et al. UBE1L is a retinoid targe t that triggers PML/RARalpha degradation and apoptosis in acute promyelocytic leukemia. Proc Natl Acad Sci USA 2002;99(6):3806–11.

80. Park D.J., Chumakov A.M., Vuong P.T. et al. CCAAT/enhancer binding protein epsilon is a potential retinoid target gene in acute promyelocytic leukemia treatment. J Clin Invest 1999;103(10): 1399–408.

81. Pratt M.A., Niu M., White D. Differential regulation of protein expression , growth and apoptosis by natural and synthetic retinoids. J Cell Biochem 2003;90(4):692–708.

82. Raffo P., Emionite L., Colucci L. et al. Retinoid receptors: pathways of pr oliferation inhibition and apoptosis induction in breast cancer cell lines. Anticancer Res 2000;20(3A):1535–43.

83. Calmon M.F., Rodrigues R.V., Kaneto C.M. et al. Epigenetic silencing of CRAB P2 and MX1 in head and neck tumors. Neoplasia 2009;11(12):1329–39.

84. Campos B., Centner F.S., Bermejo J.L. et al. Aberrant expression of retinoic acid signaling molecules influences patient survival in astrocytic gliomas. Am J Pathol 2011;178(5):1953–64.

85. Pavone M.E., Reierstad S., Sun H. et al. Altered retinoid uptake and action co ntributes to cell survival in endometriosis. J Clin Endocrinol Metab 2010;95(11):E300–9.

86. Favorskaya I., Kainov Y., Chemeris G. et al. Expression and clinical significan ce of CRABP1 and CRABP2 in non-small cell lung cancer. Tumour Biol 2014;35(10):10295–300.

87. Bertucci F., Houlgatte R., Benziane A. et al. Gene expression profiling of primary breast carcinomas using arrays of candidate genes. Hum Mol Genet 2000;9(20):2981–91.

88. Tsibris J.C., Segars J., Coppola D. et al. Insights from gene arrays on the development and growth regulation of uterine leiomyomata. Fertil Steril 2002;78(1):114–21.

89. Delva L., Cornic M., Balitrand N. et al. Resistance to all-trans retinoic acid (AT RA) therapy in relapsing acute promyelocytic leukemia: study of in vitro ATRA sensitivity and cellular retinoic acid binding protein levels in leukemic cells. Blood 1993;82(7):2175–81.

90. Zhou D.C., Hallam S.J., Lee S.J. et al. Constitutive expression of cellular retinoic acid binding protein II and lack of correlation with sensitivity to all-trans retinoic acid in acute promyelocytic leukemia cells. Cancer Res 1998;58(24):5770–6.

91. Jin B.Y., Fu G.H., Jiang X. et al. CRABP2 and FABP5 identified by 2D DIGE profiling are upregulated in human bladder cancer. Chin Med J (Engl) 2013;126(19):3787–9.

92. Mallikarjuna K., Sundaram C.S., Sharma Y. et al. Comparative proteomic analysis of differentially expressed proteins in primary retinoblastoma tumors. Proteomics Clin Appl 2010;4(4):449–63.

93. Vo H.P., Crowe D.L. 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(1A):217–24.

94. Hathout Y., Riordan K., Gehrmann M., Fenselau C. Differential protein expression in the cytosol fraction of an MCF-7 breast cancer cell line selected for resistance toward melphalan. J Proteome Res 2002;1(5):435–42.

95. Vreeland A.C., Levi L., Zhang W. et al. Cellular retinoic acid-binding protein 2 inhibits tumor growth by two distinct mechanisms. J Biol Chem 2014;289(49): 34065–73.

96. Hinman M.N., Lou H. Diverse molecular functions of Hu proteins. Cell Mol Life Sci 2008;65 (20):3168–81.

97. Brennan C.M., Steitz J.A. HuR and mRNA stability. Cell Mol Life Sci 2001;58(2):266–77.

98. Chen C.Y., Xu N., Shyu A.B. Highly selective actions of HuR in antagonizing AUrich element -mediated mRNA destabilization. Mol Cell Biol 2002;22(20):7268–78.

99. Lopez de Silanes I., Zhan M., Lal A. et al. Identification of a target RNA motif for RNAbin ding protein HuR. Proc Natl Acad Sci USA 2004;101(9):2987–92.

100. Gupta A., Williams B.R., Hanash S.M., Rawwas J. Cellular retinoic acid-binding protein II is a direct transcriptional target of MycN in neuroblastoma. Cancer Res 2006;66(16):8100–8.

101. Ruff S.J., Ong D.E. Cellular retinoic acid binding protein is associated with mitochondria. F EBS Lett 2000;487(2):282–6.

102. Levadoux-Martin M., Li Y., Blackburn A. et al. Perinuclear localisation of cellular retinoic a cid binding protein I mRNA. Biochem Biophys Res Commun 2006;340(1):326–31.

103. Gaub M.P., Lutz Y., Ghyselinck N.B. et al. Nuclear detection of cellular retinoic acid binding proteins I and II with new antibodies. J Histochem Cytochem 1998;46(10):1103–11.

104. Jing Y., Waxman S., Mira-y-Lopez R. The cellular retinoic acid binding protein II is a positive regulator of retinoic acid signaling in breast cancer cells. Cancer Res 1997;57(9):1668–72.

105. Budhu A., Gillilan R., Noy N. Localization of the RAR interaction domain of cellular retinoic aci d binding protein-II. J Mol Biol 2001;305(4):939–49.

106. Noy N. Retinoid-binding proteins: mediators of retinoid action. Biochem J 2000;348 Pt 3:481–95.

107. Fiorella P.D., Napoli J.L. Expression of cellular retinoic acid binding protein (CRABP) in Escheric hia coli. Characterization and evidence that holo-CRABP is a substrate in retinoic acid metabolism. J Biol Chem 1991;266(25):16572–9.

108. Napoli J.L. Interactions of retinoid binding proteins and enzymes in retinoid metabolism. Biochim Biophys Acta 1999;1440(2–3):139–62.

109. Napoli J.L., Posch K.P., Fiorella P.D., Boerman M.N. Physiological occurrence, biosynthesis and metabo lism of retinoic acid: evidence for roles of cellular retinol-binding

110. protein (CRBP) and cellular retinoic acidbinding protein (CRABP) in the pathway of retinoic acid homeostasis. Biomed Pharmacother 1991;45(4–5):131–43.

111. Boylan J.F., Gudas L.J. The level of CRABP-I expression influences the amounts and types of all-trans-re tinoic acid metabolites in F9 teratocarcinoma stem cells. J Biol Chem 1992;267(30):21486–91.

112. Boylan J.F., Gudas L.J. Overexpression of the cellular retinoic acid binding protein-I (CRABP-I) results in a reduction in differentiation-specific gene expression in F9 teratocarcinoma cells. J Cell Biol 1991;112(5):965–79.

113. Won J.Y., Nam E.C., Yoo S.J. et al. The effect of cellular retinoic acid binding protein-I

114. expression on t he CYP26-mediated catabolism of all-trans retinoic acid and cell proliferation in head and neck squamous cell carcinoma. Metabolism 2004;53(8):1007–12.

115. Tang X.H., Vivero M., Gudas L.J. Overexpression of CRABPI in suprabasal keratinocytes enhances the prolifer ation of epidermal basal keratinocytes in mouse skin topically treated with all-trans retinoic acid. Exp Cell Res 2008;314(1):38–51.

116. Chen A.C., Yu K., Lane M.A., Gudas L.J. Homozygous deletion of the CRABPI gene in AB1 embryonic stem cells r esults in increased CRABPII gene expression and decreased intracellular retinoic acid concentration. Arch Biochem Biophys 2003;411(2):159–73.

117. Venepally P., Reddy L.G., Sani B.P. Analysis of the effects of CRABP I expression on the RA-induced transcription mediated by retinoid receptors. Biochemistry 1996;35(31):9974–82.

118. Persaud S.D., Lin Y.W., Wu C.Y. et al. Cellular retinoic acid binding protein I mediates rapid non-canonical a ctivation of ERK1/2 by all-trans retinoic acid. Cell Signal 2013;25(1):19–25.

119. Kainov Y., Favorskaya I., Delektorskaya V. et al. CRABP1 provides high malignancy of transformed mesenchymal cells and contributes to the pathogenesis of mesenchymal and neuroendocrine tumors. Cell Cycle 2014;13(10):1530–9.

120. Lind G.E., Kleivi K., Meling G.I. et al. ADAMTS1, CRABP1, and NR3C1 identified as epigenetically deregulated genes in colorectal tumorigenesis. Cell Oncol 2006;28(5–6):259–72.

121. Lee H.S., Kim B.H., Cho N.Y. et al. Prognostic implications of and relationship between CpG island hypermethylation and repetitive DNA hypomethylation in hepatocellular carcinoma. Clin Cancer Res 2009;15(3):812–20.

122. Tanaka K., Imoto I., Inoue J. et al. Frequent methylation-associated silencing of a candidate tumor-suppressor, CRA BP1, in esophageal squamous-cell carcinoma. Oncogene 2007;26(44):6456–68.

123. Huang Y., de la Chapelle A., Pellegata N.S. Hypermethylation, but not LOH, is associated with the low expression of MT1G and CRABP1 in papillary thyroid carcinoma. Int J Cancer 2003;104(6):735–44.

124. Hawthorn L., Stein L., Varma R. et al. TIMP1 and SERPIN-A overexpression and TFF3 and CRABP1 underexpression as bioma rkers for papillary thyroid carcinoma. Head Neck 2004;26(12):1069–83.

125. Fontaine J.F., Mirebeau-Prunier D., Raharijaona M. et al. Increasing the number of thyroid lesions classes in microarr ay analysis improves the relevance of diagnostic markers. PloS One 2009;4(10):e7632.

126. Pfoertner S., Goelden U., Hansen W. et al. Cellular retinoic acid binding protein I: expression and functional influen ce in renal cell carcinoma. Tumour Biol 2005;26(6): 313–23.

127. Miyake T., Ueda Y., Matsuzaki S. et al. CRABP1-reduced expression is associated with poorer prognosis in serous and cle ar cell ovarian adenocarcinoma. J Cancer Res Clin Oncol 2011;137(4):715–722.

128. Lu Y., Lemon W., Liu P.Y. et al. A gene expression signature predicts survival of patients with stage I non-small cell lung cancer. PLoS Med 2006;3(12):e467.

129. Wu X., Blanck A., Norstedt G. et al. Identification of genes with higher expression in human uterine leiomyomas than in the corresponding myometrium. Mol Hum Reprod 2002;8(3):246–54.

130. Banz C., Ungethuem U., Kuban R.J. et al. The molecular signature of endometriosis-associated endometrioid ovarian cancer differs significantly from endometriosis-independent endometrioid ovarian cancer. Fertil Steril 2010;94(4):1212–7.

131. Ishibe T., Nakayama T., Aoyama T. et al. Neuronal differentiation of synovial sarcoma and its therapeutic application. Clin Orthop Relat Res 2008;466(9):2147–55.

132. Perez-Castro A.V., Tran V.T., NguyenHuu M.C. Defective lens fiber differentiation and pancreatic tumorigenesis caused by e ctopic expression of the cellular retinoic acid-binding protein I. Development 1993;119(2):363–75.