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Gene regulation in cancer. human retroviral infectionsOur laboratory is interested in the roles of altered gene expression in human cancer and in human retroviral infections. One set of projects focuses on the controls of gene expression of HIV and of the human T cell leukemia virus type 1 (HTLV-1) in infected T cells. We have previously demonstrated the important roles of the NF-kappaB transcription factors in the activation of latent HIV infection. More recently. we identified models of latent HTLV-1 infection and have shown that immune activation stimuli will induce HTLV gene expression. This suggests important models for the activation of HTLV during disease pathogenesis. Other experiments in the laboratory have focused on the roles of the NF-kappaB transcription factors in human cancer. We have identified mutations of the NF-kB-2 gene that occur in 5-30% of human cutaneous T cell lymphomas and are associated with altered transcriptional regulation leading to increased T cell activation. proliferation. and survival. that may contribute to T cell lymphomagenesis. We have also observed very high levels of constitutive NF-kB activation in androgen-independent human prostate cancer cell lines and are studying the responsible mechanisms as well as the consequences for prostate cancer progression. Selected PublicationsZheng X, Chang RL, Cui XX, Avila G, Huang MT, Liu Y, Kong AN, Rabson AB, Conney AH. (2008) Inhibition of NF-kappaB by (E)3-[(4-methylphenyl)-sulfonyl]-2-propenenitrile (BAY11-7082; BAY) is associated with enhanced 12-O-tetradecanoylphorbol-13-acetate-induced growth suppression and apoptosis in human prostate cancer PC-3 cells. Int J Oncol. 32(1):257-64. Banerjee D, Glod J, Rabson AB. (2007) The Raz mTaz of human mesenchymal stem cells. Marín YE, Wall BA, Wang S, Namkoong J, Martino JJ, Suh J, Lee HJ, Rabson AB, Yang CS, Chen S, Ryu JH. (2007) Curcumin downregulates the constitutive activity of NF-kappaB and induces apoptosis in novel mouse melanoma cells. Melanoma Res. 17(5):274-83. Zheng X, Cui XX, Avila GE, Huang MT, Liu Y, Patel J, Kong AN, Paulino R, Shih WJ, Lin Y, Rabson AB, Reddy BS, Conney AH. (2007) Atorvastatin and celecoxib inhibit prostate PC-3 tumors in immunodeficient mice. Clin Cancer Res. 13(18 Pt 1):5480-7. Xiao G. Rabson AB. Young W. Qing G. Qu Z. (2006) Alternative pathways of NF-kappaB activation: A double-edged sword in health and disease. Cytokine Growth Factor Rev. 17(4):281-93. Zheng X. Chang RL. Cui XX. Avila GE. Hebbar V. Garzotto M. Shih WJ. Lin Y. Lu SE. Rabson AB. Kong AN. Conney AH. (2006) Effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination with paclitaxel (Taxol) on prostate Cancer LNCaP cells cultured in vitro or grown as xenograft tumors in immunodeficient mice. Clin Cancer Res. 12(11 Pt 1):3444-51. Wan L. Zhang X. Gunaseelan S. Pooyan S. Debrah O. Leibowitz MJ. Rabson AB. Stein S. Sinko PJ. (2006) Novel multi-component nanopharmaceuticals derived from poly(ethylene) glycol. retro-inverso-Tat nonapeptide and saquinavir demonstrate combined anti-HIV effects. AIDS Res Ther. 3:12. Gu X. Ke S. Liu D. Sheng T. Thomas PE. Rabson AB. Gallo MA. Xie W. Tian Y. (2006) Role of NF-{kappa}B in Regulation of PXR-mediated Gene Expression: A mechanism for the Suppression of Cytochrome P-450 3A4 by Proinflammatory agents. J Biol Chem. 281(26):17882-9. Medina DJ. Sheay W. Osman M. Goodell L. Martin J. Rabson AB. Strair RK. (2005) Adenovirus infection and cytotoxicity of primary mantle cell lymphoma cells. Exp Hematol. 33(11):1337-47. Hansson A. Marin YE. Suh J. Rabson AB. Chen S. Huberman E. Chang RL. Conney AH. Zheng X. (2005) Enhancement of TPA-induced growth inhibition and apoptosis in myeloid leukemia cells by BAY 11-7082. an NF-kappaB inhibitor. Int J Oncol. 27(4):941-8. Zhao Y. Ramakrishnan A. Kim KE. Rabson AB. (2005) Regulation of Bcl-3 through interaction with the Lck tyrosine kinase. Biochem Biophys Res Commun. 335(3):865-73. Avila GE. Zheng X. Cui XX. Ryan AD. Hansson A. Suh J. Rabson AB. Chang RL. Shih WJ. Lin Y. Crowell P. Lu YP. Lou YR. Conney AH. (2005) Inhibitory effects of 12-O-tetradecanoylphorbol-13-acetate alone or in combination with all-trans retinoic acid on the growth of cultured human pancreas cancer cells and pancreas tumor xenografts in immunodeficient mice. J Pharmacol Exp Ther. 315(1):170-87. Lin. H.-C.. Hickey. M.. Hsu. L.. Medina. D.. and Rabson. A.B. (2005). Activation of human T-Cell leukemia virus Type 1 LTR and cellular promoters by T-Cell receptor signaling and HTLV-1 tax expression. In press. Virology. Rabson. A.B. and Weissman. D. (2005) From microarray to bedside: targeting NF-κB for therapy of lymphomas. Clinical Cancer Research. 11:2-5. Suh. J. and Rabson. A.B. (2004) NF-kappaB activation in Human Prostate Cancer: Important Mediator or Epiphenomenon? J. Cellular Biochem. 91:100-117. Suh. J.S.. Payvandi. F.. Edelstein. L.C.. Amenta. P.S.. Zong. W.-X.. Gélinas. C.. and Rabson. A.B. (2002). Mechanisms of constitutive NF-kB activation in human prostate cancer cells. The Prostate. 52:183-200. Ke. S. Rabson A.B.. Germino J.F.. Gallo M.A.. and Tian Y. (2001). Mechanism of suppression of Cytochrome P-450 1A1 expression by tumor necrosis Factor-alpha and Lipopolysaccharide. J. Biol. Chem. 276:39638-39644. Rabson. A.B. and Lin. H.-C. (2000). NF-kappaB and HIV: Linking viral and immune activation. Adv. Pharm. 48: 161-207. Kim. K.-E.. Gu. C.. Thakur. S.. Vieira. E.. Lin. J.C.. and Rabson. A.B. (2000) Transcriptional regulatory effects of lymphoma-associated NFKB2/lyt10 protooncogenes. Oncogene 19: 1334-1345. |
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