Matusik Lab

In North America, one in ten men is diagnosed with prostate cancer.  Prostate cancer starts as an androgen dependent disease that progresses to an androgen independent cancer.  The androgen independent tumors fail therapy.  One of the major impediments to prostate cancer research is that no appropriate animal model system adequately displays the recognized stages of human prostatic disease.  Further, no new therapeutic approaches have been developed after current therapy fails.  Our laboratory has developed the probasin (PB) gene as a model system for androgen action, to establish new transgenic animal models for prostate cancr, and to test new therapeutic approaches for treatment.  The androgen receptor (AR) can function through similar cis-acting DNA elements similar to the palindromic glucocorticoid response element; however, recent data has shown that distinct AR elements (ARE) exist and function via cooperative interactions of multiple elements in the PB promoter.  Further, since the PB promoter directs prostate specific expression in transgenic mice, it has become a model to dissect the key cis-acting DNA elements that control prostate-specific gene expression.  Our laboratory has designed new PB promoters that target high levels of transgene expression to the prostate. These new promoters now serve to create new animal models for prostate cancer and to develop gene therapy vectors that will target a therapeutic gene(s) in the treatment of prostate cancer.  The PB promoter has been linked to oncogenes and growth factors to create new transgenic mouse models for prostate cancer.  Transgenic mice carrying PB-oncogenes develop various stages of disease including prostatic precursor lesions that advance to an adenocarcinoma and then to high grade metastatic cancer.  Gene expression profiles are being analyzed in these animal models to identify the key genes involved in tumor progression.  By identifying the genes that are responsible for tumor progression, we can develop new targets for therapeutic intervention.This is default text for the community description. This community's Chief or Leader(s) can modify it by editing this page.

Publications

Featured publications

  1. SKP2 inactivation suppresses prostate tumorigenesis by mediating JARID1B ubiquitination. Lu W, Liu S, Li B, Xie Y, Adhiambo C, Yang Q, Ballard BR, Nakayama KI, Matusik RJ, Chen Z (2015) Oncotarget 6(2): 771-88
    › Primary publication · 25596733 (PubMed) · PMC4359254 (PubMed Central)
  2. Inhibition of NF-kappa B signaling restores responsiveness of castrate-resistant prostate cancer cells to anti-androgen treatment by decreasing androgen receptor-variant expression. Jin R, Yamashita H, Yu X, Wang J, Franco OE, Wang Y, Hayward SW, Matusik RJ (2015) Oncogene 34(28): 3700-10
    › Primary publication · 25220414 (PubMed) · PMC4362792 (PubMed Central)
  3. Activation of Wnt/β-catenin signaling in a subpopulation of murine prostate luminal epithelial cells induces high grade prostate intraepithelial neoplasia. Valkenburg KC, Yu X, De Marzo AM, Spiering TJ, Matusik RJ, Williams BO (2014) Prostate 74(15): 1506-20
    › Primary publication · 25175604 (PubMed) · PMC4175140 (PubMed Central)
  4. SOX2 expression in the developing, adult, as well as, diseased prostate. Yu X, Cates JM, Morrissey C, You C, Grabowska MM, Zhang J, DeGraff DJ, Strand DW, Franco OE, Lin-Tsai O, Hayward SW, Matusik RJ (2014) Prostate Cancer Prostatic Dis 17(4): 301-9
    › Primary publication · 25091041 (PubMed) · PMC4227931 (PubMed Central)
  5. Slug regulates E-cadherin repression via p19Arf in prostate tumorigenesis. Xie Y, Liu S, Lu W, Yang Q, Williams KD, Binhazim AA, Carver BS, Matusik RJ, Chen Z (2014) Mol Oncol 8(7): 1355-64
    › Primary publication · 24910389 (PubMed) · PMC4198473 (PubMed Central)
  6. FOXA1 deletion in luminal epithelium causes prostatic hyperplasia and alteration of differentiated phenotype. DeGraff DJ, Grabowska MM, Case TC, Yu X, Herrick MK, Hayward WJ, Strand DW, Cates JM, Hayward SW, Gao N, Walter MA, Buttyan R, Yi Y, Kaestner KH, Matusik RJ (2014) Lab Invest 94(7): 726-39
    › Primary publication · 24840332 (PubMed) · PMC4451837 (PubMed Central)
  7. NFI transcription factors interact with FOXA1 to regulate prostate-specific gene expression. Grabowska MM, Elliott AD, DeGraff DJ, Anderson PD, Anumanthan G, Yamashita H, Sun Q, Friedman DB, Hachey DL, Yu X, Sheehan JH, Ahn JM, Raj GV, Piston DW, Gronostajski RM, Matusik RJ (2014) Mol Endocrinol 28(6): 949-64
    › Primary publication · 24801505 (PubMed) · PMC4042066 (PubMed Central)
  8. NF-κB gene signature predicts prostate cancer progression. Jin R, Yi Y, Yull FE, Blackwell TS, Clark PE, Koyama T, Smith JA, Matusik RJ (2014) Cancer Res 74(10): 2763-72
    › Primary publication · 24686169 (PubMed) · PMC4024337 (PubMed Central)
  9. Mouse models of prostate cancer: picking the best model for the question. Grabowska MM, DeGraff DJ, Yu X, Jin RJ, Chen Z, Borowsky AD, Matusik RJ (2014) Cancer Metastasis Rev 33(2-3): 377-97
    › Primary publication · 24452759 (PubMed) · PMC4108581 (PubMed Central)
  10. Skp2 regulates androgen receptor through ubiquitin-mediated degradation independent of Akt/mTOR pathways in prostate cancer. Li B, Lu W, Yang Q, Yu X, Matusik RJ, Chen Z (2014) Prostate 74(4): 421-32
    › Primary publication · 24347472 (PubMed) · PMC4062570 (PubMed Central)

Community Leaders

Contact Information

1161 21st Ave. S.
1302 MCN
Nashville, TN 37232
USA

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Keywords & MeSH Terms

MeSH terms are retrieved from PubMed records. Learn more.

Key: MeSH Term Keyword

Androgen Antagonists Apoptosis cancer Carcinoma, Squamous Cell chromatin Cluster Analysis developmental biology Disease Progression endocrinology fertility gene regulation gene therapy genetics genome genomics Growth Substances Half-Life Haplorhini Homeodomain Proteins Humans mouse receptor Mutation NFI Transcription Factors Nuclear Proteins Phosphorylation Proteins proteomics Real-Time Polymerase Chain Reaction receptor recombination reproduction Substrate Specificity Tamoxifen Thymidine Kinase transcription transcription factor transformation Transplantation, Heterologous