DF/HCC Program Affiliation

Cancer Immunology
Prostate Cancer

Research Abstract

The major focus of the lab is on the molecular basis of prostate cancer development and progression. The androgen receptor, which is a member of the steroid hormone receptor superfamily, plays a major role in prostate cancer. We have identified mutations in the androgen receptor that contribute to prostate cancer progression and are characterizing androgen receptor interacting proteins. We have also determined that the platelet derived growth factor receptor contributes to prostate cancer and are attempting to define other important growth factor-receptor interactions that may be useful therapeutic targets. Finally, efforts are underway to develop murine transgenic and gene knockout models of PCa. A second interest in the lab is a novel T cell population termed NK T cells and the MHC class I-like CD1d protein they recognize. These cells appear to have an important immunoregulatory function and we are determining the role they play in viral infections and anti-tumor
responses.

Publications

• Stanbrough M, Bubley GJ, Ross K, Golub TR, Rubin MA, Penning TM, Febbo PG, Balk SP.Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer.Cancer Res 2006 Mar 1;66(5):2815-25.
  16510604
• Exley MA, He Q, Cheng O, Wang RJ, Cheney CP, Balk SP, Koziel MJ.Cutting edge: Compartmentalization of Th1-like noninvariant CD1d-reactive T cells in hepatitis C virus-infected liver.J Immunol 2002 Feb 15;168(4):1519-23.
  11823474
• Taplin ME, Bubley GJ, Ko YJ, Small EJ, Upton M, Rajeshkumar B, Balk SP.Selection for androgen receptor mutations in prostate cancers treated with androgen antagonist.Cancer Res 1999 Jun 1;59(11):2511-5.
  10363963
• Exley M, Porcelli S, Furman M, Garcia J, Balk S.CD161 (NKR-P1A) costimulation of CD1d-dependent activation of human T cells expressing invariant V alpha 24 J alpha Q T cell receptor alpha chains.J Exp Med 1998 Sep 7;188(5):867-76.
  9730888
• Taplin ME, Manola J, Oh WK, Kantoff PW, Bubley GJ, Smith M, Barb D, Mantzoros C, Gelmann EP, Balk SP.A phase II study of mifepristone (RU-486) in castration-resistant prostate cancer, with a correlative assessment of androgen-related hormones.BJU Int 2008
  18399827
• Wang H, Leav I, Ibaragi S, Wegner M, Hu GF, Lu ML, Balk SP, Yuan X.SOX9 is expressed in human fetal prostate epithelium and enhances prostate cancer invasion.Cancer Res 2008 Mar 15;68(6):1625-30.
  18339840
• Balk SP, Knudsen KE.AR, the cell cycle, and prostate cancer.Nucl Recept Signal 2008;6:e001.
  18301781
• Barb D, Neuwirth A, Mantzoros CS, Balk SP.Adiponectin signals in prostate cancer cells through Akt to activate the mammalian target of rapamycin pathway.Endocr Relat Cancer 2007 Dec;14(4):995-1005.
  18045951
• Jiang X, Borgesi RA, McKnight NC, Kaur R, Carpenter CL, Balk SP.Activation of nonreceptor tyrosine kinase Bmx/Etk mediated by phosphoinositide 3-kinase, epidermal growth factor receptor, and ErbB3 in prostate cancer cells.J Biol Chem 2007 Nov 9;282(45):32
  17823122
• Hodgson MC, Astapova I, Hollenberg AN, Balk SP.Activity of androgen receptor antagonist bicalutamide in prostate cancer cells is independent of NCoR and SMRT corepressors.Cancer Res 2007 Sep 1;67(17):8388-95.
  17804755
• van der Vliet HJ, Koon HB, Atkins MB, Balk SP, Exley MA.Exploiting regulatory T-cell populations for the immunotherapy of cancer.J Immunother 2007 Sep;30(6):591-5.
  17667522
• Li H, Bubley GJ, Balk SP, Gaziano JM, Pollak M, Stampfer MJ, Ma J.Hypoxia-inducible factor-1alpha (HIF-1alpha) gene polymorphisms, circulating insulin-like growth factor binding protein (IGFBP)-3 levels and prostate cancer.Prostate 2007 Sep 1;67(12):1354-
  17624927
• van Dervliet HJ, Koon HB, Yue SC, Uzunparmak B, Seery V, Gavin MA, Rudensky AY, Atkins MB, Balk SP, Exley MA.Effects of the administration of high-dose interleukin-2 on immunoregulatory cell subsets in patients with advanced melanoma and renal cell cancer
  17404092
• Reddy GK, Balk SP.Clinical utility of microarray-derived genetic signatures in predicting outcomes in prostate cancer.Clin Genitourin Cancer 2006 Dec;5(3):187-9.
  17239271
• Wang H, McKnight NC, Zhang T, Lu ML, Balk SP, Yuan X.SOX9 is expressed in normal prostate basal cells and regulates androgen receptor expression in prostate cancer cells.Cancer Res 2007 Jan 15;67(2):528-36.
  17234760
• Masiello D, Mohi MG, McKnight NC, Smith B, Neel BG, Balk SP, Bubley GJ.Combining an mTOR Antagonist and Receptor Tyrosine Kinase Inhibitors for the Treatment of Prostate Cancer.Cancer Biol Ther 2007 Feb;6(2):195-201.
  17218776
• van der Vliet HJ, Balk SP, Exley MA.Natural killer T cell-based cancer immunotherapy.Clin Cancer Res 2006 Oct 15;12(20 Pt 1):5921-3.
  17062661
• Chen S, Xu Y, Yuan X, Bubley GJ, Balk SP.Androgen receptor phosphorylation and stabilization in prostate cancer by cyclin-dependent kinase 1.Proc Natl Acad Sci U S A 2006 Oct 24;103(43):15969-74.
  17043241
• Cai C, Chen SY, Zheng Z, Omwancha J, Lin MF, Balk SP, Shemshedini L.Androgen regulation of soluble guanylyl cyclasealpha1 mediates prostate cancer cell proliferation.Oncogene 2007 Mar 8;26(11):1606-15.
  16964290
• Xu Y, Chen SY, Ross KN, Balk SP.Androgens induce prostate cancer cell proliferation through mammalian target of rapamycin activation and post-transcriptional increases in cyclin D proteins.Cancer Res 2006 Aug 1;66(15):7783-92.
  16885382
• Yuan X, Li T, Wang H, Zhang T, Barua M, Borgesi RA, Bubley GJ, Lu ML, Balk SP.Androgen receptor remains critical for cell-cycle progression in androgen-independent CWR22 prostate cancer cells.Am J Pathol 2006 Aug;169(2):682-96.
  16877366
• Ilyinskii PO, Wang R, Balk SP, Exley MA.CD1d mediates T-cell-dependent resistance to secondary infection with encephalomyocarditis virus (EMCV) in vitro and immune response to EMCV infection in vivo.J Virol 2006 Jul;80(14):7146-58.
  16809320
• Chen SY, Wulf G, Zhou XZ, Rubin MA, Lu KP, Balk SP.Activation of beta-catenin signaling in prostate cancer by peptidyl-prolyl isomerase Pin1-mediated abrogation of the androgen receptor-beta-catenin interaction.Mol Cell Biol 2006 Feb;26(3):929-39.
  16428447
• Sonoda KH, Sakamoto T, Qiao H, Hisatomi T, Oshima T, Tsutsumi-Miyahara C, Exley M, Balk SP, Taniguchi M, Ishibashi T.The analysis of systemic tolerance elicited by antigen inoculation into the vitreous cavity: vitreous cavity-associated immune deviation.I
  16236129
• Yue SC, Shaulov A, Wang R, Balk SP, Exley MA.CD1d ligation on human monocytes directly signals rapid NF-kappaB activation and production of bioactive IL-12.Proc Natl Acad Sci U S A 2005 Aug 16;102(33):11811-6.
  16091469
• Nieuwenhuis EE, Gillessen S, Scheper RJ, Exley MA, Taniguchi M, Balk SP, Strominger JL, Dranoff G, Blumberg RS, Wilson SB.CD1d and CD1d-restricted iNKT-cells play a pivotal role in contact hypersensitivity.Exp Dermatol 2005 Apr;14(4):250-8.
  15810882
• Fu XS, Choi E, Bubley GJ, Balk SP.Identification of hypoxia-inducible factor-1alpha (HIF-1alpha) polymorphism as a mutation in prostate cancer that prevents normoxia-induced degradation.Prostate 2005 May 15;63(3):215-21.
  15538748
• Exley MA, Bigley NJ, Cheng O, Shaulov A, Tahir SM, Carter QL, Garcia J, Wang C, Patten K, Stills HF, Alt FW, Snapper SB, Balk SP.Innate immune response to encephalomyocarditis virus infection mediated by CD1d.Immunology 2003 Dec;110(4):519-26.
  14632651
• Spentzos D, Mantzoros C, Regan MM, Morrissey ME, Duggan S, Flickner-Garvey S, McCormick H, DeWolf W, Balk S, Bubley GJ.Minimal effect of a low-fat/high soy diet for asymptomatic, hormonally naive prostate cancer patients.Clin Cancer Res 2003 Aug 15;9(9):3
  12960113
• Rossi S, Graner E, Febbo P, Weinstein L, Bhattacharya N, Onody T, Bubley G, Balk S, Loda M.Fatty acid synthase expression defines distinct molecular signatures in prostate cancer.Mol Cancer Res 2003 Aug;1(10):707-15.
  12939396
• Gillessen S, Naumov YN, Nieuwenhuis EE, Exley MA, Lee FS, Mach N, Luster AD, Blumberg RS, Taniguchi M, Balk SP, Strominger JL, Dranoff G, Wilson SB.CD1d-restricted T cells regulate dendritic cell function and antitumor immunity in a granulocyte-macrophage
  12847287
• Amir AL, Barua M, McKnight NC, Cheng S, Yuan X, Balk SP.A direct beta-catenin-independent interaction between androgen receptor and T cell factor 4.J Biol Chem 2003 Aug 15;278(33):30828-34.
  12799378
• Balk SP, Ko YJ, Bubley GJ.Biology of prostate-specific antigen.J Clin Oncol 2003 Jan 15;21(2):383-91.
  12525533
• Bubley GJ, Balk SP, Regan MM, Duggan S, Morrissey ME, Dewolf WC, Salgami E, Mantzoros C.Serum levels of insulin-like growth factor-1 and insulin-like growth factor-1 binding proteins after radical prostatectomy.J Urol 2002 Nov;168(5):2249-52.
  12394769
• Boyson JE, Rybalov B, Koopman LA, Exley M, Balk SP, Racke FK, Schatz F, Masch R, Wilson SB, Strominger JL.CD1d and invariant NKT cells at the human maternal-fetal interface.Proc Natl Acad Sci U S A 2002 Oct 15;99(21):13741-6.
  12368486
• Carroll PR, Kantoff PW, Balk SP, Brown MA, D'amico AV, George DJ, Grossfeld GD, Johnson CS, Kelly WK, Klotz L, Lee WR, Lubeck DP, Mcleod DG, Oh WK, Pollack A, Sartor O, Smith MR, Hart C,.Overview consensus statement. Newer approaches to androgen deprivati
  12231036
• Masiello D, Cheng S, Bubley GJ, Lu ML, Balk SP.Bicalutamide functions as an androgen receptor antagonist by assembly of a transcriptionally inactive receptor.J Biol Chem 2002 Jul 19;277(29):26321-6.
  12015321
• Exley MA, Tahir SM, Cheng O, Shaulov A, Joyce R, Avigan D, Sackstein R, Balk SP.A major fraction of human bone marrow lymphocytes are Th2-like CD1d-reactive T cells that can suppress mixed lymphocyte responses.J Immunol 2001 Nov 15;167(10):5531-4.
  11698421
• Tahir SM, Cheng O, Shaulov A, Koezuka Y, Bubley GJ, Wilson SB, Balk SP, Exley MA.Loss of IFN-gamma production by invariant NK T cells in advanced cancer.J Immunol 2001 Oct 1;167(7):4046-50.
  11564825
• Stanbrough M, Leav I, Kwan PW, Bubley GJ, Balk SP.Prostatic intraepithelial neoplasia in mice expressing an androgen receptor transgene in prostate epithelium.Proc Natl Acad Sci U S A 2001 Sep 11;98(19):10823-8.
  11535819
• Exley MA, Bigley NJ, Cheng O, Tahir SM, Smiley ST, Carter QL, Stills HF, Grusby MJ, Koezuka Y, Taniguchi M, Balk SP.CD1d-reactive T-cell activation leads to amelioration of disease caused by diabetogenic encephalomyocarditis virus.J Leukoc Biol 2001 May;6
  11358978
• Ko YJ, Small EJ, Kabbinavar F, Chachoua A, Taneja S, Reese D, DePaoli A, Hannah A, Balk SP, Bubley GJ.A multi-institutional phase ii study of SU101, a platelet-derived growth factor receptor inhibitor, for patients with hormone-refractory prostate cancer.
  11309325
• Exley M, Garcia J, Wilson SB, Spada F, Gerdes D, Tahir SM, Patton KT, Blumberg RS, Porcelli S, Chott A, Balk SP.CD1d structure and regulation on human thymocytes, peripheral blood T cells, B cells and monocytes.Immunology 2000 May;100(1):37-47.
  10809957
• Sonoda KH, Exley M, Snapper S, Balk SP, Stein-Streilein J.CD1-reactive natural killer T cells are required for development of systemic tolerance through an immune-privileged site.J Exp Med 1999 Nov 1;190(9):1215-26.
  10544194
• Fenton MA, Shuster TD, Fertig AM, Taplin ME, Kolvenbag G, Bubley GJ, Balk SP.Functional characterization of mutant androgen receptors from androgen-independent prostate cancer.Clin Cancer Res 1997 Aug;3(8):1383-8.
  9815822
• Joyce S, Woods AS, Yewdell JW, Bennink JR, De Silva AD, Boesteanu A, Balk SP, Cotter RJ, Brutkiewicz RR.Natural ligand of mouse CD1d1: cellular glycosylphosphatidylinositol.Science 1998 Mar 6;279(5356):1541-4.
  9488653
• Wilson SB, Kent SC, Patton KT, Orban T, Jackson RA, Exley M, Porcelli S, Schatz DA, Atkinson MA, Balk SP, Strominger JL, Hafler DA.Extreme Th1 bias of invariant Valpha24JalphaQ T cells in type 1 diabetes.Nature 1998 Jan 8;391(6663):177-81.
  9428763
• Sun Z, Pan J, Balk SP.Androgen receptor-associated protein complex binds upstream of the androgen-responsive elements in the promoters of human prostate-specific antigen and kallikrein 2 genes.Nucleic Acids Res 1997 Aug 15;25(16):3318-25.
  9241247
• Koningsberger JC, Chott A, Logtenberg T, Wiegman LJ, Blumberg RS, van Berge Henegouwen GP, Balk SP.TCR expression in human fetal intestine and identification of an early T cell receptor beta-chain transcript.J Immunol 1997 Aug 15;159(4):1775-82.
  9257840
• Chott A, Gerdes D, Spooner A, Mosberger I, Kummer JA, Ebert EC, Blumberg RS, Balk SP.Intraepithelial lymphocytes in normal human intestine do not express proteins associated with cytolytic function.Am J Pathol 1997 Aug;151(2):435-42.
  9250156
• Exley M, Garcia J, Balk SP, Porcelli S.Requirements for CD1d recognition by human invariant Valpha24+ CD4-CD8- T cells.J Exp Med 1997 Jul 7;186(1):109-20.
  9207002
• Bubley GJ, Balk SP.Treatment of metastatic prostate cancer. Lessons from the androgen receptor.Hematol Oncol Clin North Am 1996 Jun;10(3):713-25.
  8773507
• Porcelli S, Gerdes D, Fertig AM, Balk SP.Human T cells expressing an invariant V alpha 24-J alpha Q TCR alpha are CD4- and heterogeneous with respect to TCR beta expression.Hum Immunol 1996 Jun-Jul;48(1-2):63-7.
  8824574
• Chott A, Probert CS, Gross GG, Blumberg RS, Balk SP.A common TCR beta-chain expressed by CD8+ intestinal mucosa T cells in ulcerative colitis.J Immunol 1996 Apr 15;156(8):3024-35.
  8609425
• Taplin ME, Frantz ME, Canning C, Ritz J, Blumberg RS, Balk SP.Evidence against T-cell development in the adult human intestinal mucosa based upon lack of terminal deoxynucleotidyltransferase expression.Immunology 1996 Mar;87(3):402-7.
  8778025
• Balk SP, Polischuk JE, Probert C, Stevens C, Ebert E, She J, Terhorst C, Blumberg RS.Composition of TCR-CD3 complex in human intestinal intraepithelial lymphocytes: lack of Fc epsilon RI gamma chain.Int Immunol 1995 Aug;7(8):1237-41.
  7495730
• Taplin ME, Bubley GJ, Shuster TD, Frantz ME, Spooner AE, Ogata GK, Keer HN, Balk SP.Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer.N Engl J Med 1995 May 25;332(21):1393-8.
  7723794
• Gross GG, Schwartz VL, Stevens C, Ebert EC, Blumberg RS, Balk SP.Distribution of dominant T cell receptor beta chains in human intestinal mucosa.J Exp Med 1994 Oct 1;180(4):1337-44.
  7931067
• Balk SP, Burke S, Polischuk JE, Frantz ME, Yang L, Porcelli S, Colgan SP, Blumberg RS.Beta 2-microglobulin-independent MHC class Ib molecule expressed by human intestinal epithelium.Science 1994 Jul 8;265(5169):259-62.
  7517575
• Brooks EG, Balk SP, Aupeix K, Colonna M, Strominger JL, Groh-Spies V.Human T-cell receptor (TCR) alpha/beta + CD4-CD8- T cells express oligoclonal TCRs, share junctional motifs across TCR V beta-gene families, and phenotypically resemble memory T cells.Pr
  7505446
• Porcelli S, Yockey CE, Brenner MB, Balk SP.Analysis of T cell antigen receptor (TCR) expression by human peripheral blood CD4-8- alpha/beta T cells demonstrates preferential use of several V beta genes and an invariant TCR alpha chain.J Exp Med 1993 Jul 1
  8391057
• Blumberg RS, Yockey CE, Gross GG, Ebert EC, Balk SP.Human intestinal intraepithelial lymphocytes are derived from a limited number of T cell clones that utilize multiple V beta T cell receptor genes.J Immunol 1993 Jun 1;150(11):5144-53.
  8496608
• Davis TH, Yockey CE, Balk SP.Detection of clonal immunoglobulin gene rearrangements by polymerase chain reaction amplification and single-strand conformational polymorphism analysis.Am J Pathol 1993 Jun;142(6):1841-7.
  8506952
• Blumberg RS, Terhorst C, Bleicher P, McDermott FV, Allan CH, Landau SB, Trier JS, Balk SP.Expression of a nonpolymorphic MHC class I-like molecule, CD1D, by human intestinal epithelial cells.J Immunol 1991 Oct 15;147(8):2518-24.
  1717564
• Balk SP, Bleicher PA, Terhorst C.Isolation and expression of cDNA encoding the murine homologues of CD1.J Immunol 1991 Jan 15;146(2):768-74.
  1702817
• Bleicher PA, Balk SP, Hagen SJ, Blumberg RS, Flotte TJ, Terhorst C.Expression of murine CD1 on gastrointestinal epithelium.Science 1990 Nov 2;250(4981):679-82.
  1700477
• Balk SP, Bleicher PA, Terhorst C.Isolation and characterization of a cDNA and gene coding for a fourth CD1 molecule.Proc Natl Acad Sci U S A 1989 Jan;86(1):252-6.
  2463622