 |
|
|
Thomas Jefferson University - Richard G Pestell, M.D., Ph.D.
|
|
Richard G Pestell, M.D., Ph.D.
Cancer Biology
Thomas Jefferson University
Jefferson Medical College
Associate Dean, Cancer Programs
Professor and Chairman, Department of Cancer Biology
Director, Kimmel Cancer Center at Jefferson
Vice President, Oncology Services, Thomas Jefferson University Hospital
|
|
|
|
|
Mailing Address
|
233 S. 10th St., Room 1050
Philadelphia, Pennsylvania 19107
United States
|
|
 |
|
|
Expertise and Research Interests
|
Molecular mechanisms and gene therapy of breast and prostate cancer.
Our research activities focus on understanding the mechanisms governing cell-cycle regulated gene transcription and the role of these proteins in tumorigenesis and differentiation. The cyclin D1 gene encodes a regulatory subunit of a holoenzyme that phosphorylates and inactivates the tumor suppressor protein pRB (retinoblastoma protein) resulting in release of the pRB binding proteins and transcription factors, E2Fs. Several cyclin dependent kinase inhibitors (CDKI), p16/p19 block this activity of cyclin D1. Cyclin D1 plays a critical role in tumorigenesis and differentiation.
Because the abundance of the cyclin D1 gene is rate-limiting in progression through the cell-cycle in cells that contain the pRB protein, we have delineated the molecular mechanisms regulating the cyclin D1 gene. We demonstrated that cyclin D1 kinase (CDK) activity and cyclin D1 promoter activity is induced by oncogenes (p21ras, Rac, dbl, v-src, Neu-also known as ErbB-2), growth factors and G-protein coupled receptors. The transcription factors (E2Fs,JUN/Fos, CREB, ATF2/ETS), coactivators (p300/CBP,Brg/Brm1) and scaffolding proteins (JIP1, caveolins) coordinate this induction.
Using retroviral and lentiviral expression systems we are examining the requirement for specific cyclins and CKI for induction and progression of breast and prostate tumors induced by oncogenes. These systems are used to examine treatment synergy with conventional therapies.
We have developed tissue-specific inducible transgenic expression systems and are using this transgenic approach to examine the role of cyclin D1, the CDKI in breast and prostate cancer.
Using knockout mice we are examining the role of CDKI in breast cancer induced by specific oncogenes and synergy with conventional therapies.
|
|
|
Keywords
|
|
cyclin d1; signal transduction; breast cancer; prostate cancer; gene therapy
|
|
|
Publications
|
- Selected Publications
- Fu M, Rao M, Wang C, Sakamaki T, Wang J, Di Vizio D, Zhang X, Albanese C, Balk S, Chang C, Fan S, Rosen E, Palvimo JJ, Janne OA, Muratoglu S, Avantaggiati ML, Pestell RG. Acetylation of androgen receptor enhances coactivator binding and promotes prostate cancer cell growth. Mol Cell Biol. 2003 Dec;23(23):8563-75.
- Albanese C, Hulit J, Sakamaki T, Pestell RG. Recent advances in inducible expression in transgenic mice. Semin Cell Dev Biol. 2002 Apr;13(2):129-41.
- Neumeister P, Albanese C, Balent B, Greally J, Pestell R. Senescence and epigenetic dysregulation in cancer. Int J Biochem Cell Biol. 2002 Nov;34(11):1475.
- Tanaka H, Matsumura I, Ezoe S, Satoh Y, Sakamaki T, Albanese C, Machii T, Pestell RG, Kanakura Y. E2F1 and c-Myc potentiate apoptosis through inhibition of NF-kappaB activity that facilitates MnSOD-mediated ROS elimination. Mol Cell. 2002 May;9(5):1017-29.
- Fu M, Wang C, Wang J, Zhang X, Sakamaki T, Yeung YG, Chang C, Hopp T, Fuqua SA, Jaffray E, Hay RT, Palvimo JJ, Janne OA, Pestell RG. Androgen receptor acetylation governs trans activation and MEKK1-induced apoptosis without affecting in vitro sumoylation and trans-repression function. Mol Cell Biol. 2002 May;22(10):3373-88.
- Wang C, Fu M, D''Amico M, Albanese C, Zhou JN, Brownlee M, Lisanti MP, Chatterjee VK, Lazar MA, Pestell RG. Inhibition of cellular proliferation through IkappaB kinase-independent and peroxisome proliferator-activated receptor gamma-dependent repression of cyclin D1. Mol Cell Biol. 2001 May;21(9):3057-70.
- Wang C, Fu M, Angeletti RH, Siconolfi-Baez L, Reutens AT, Albanese C, Lisanti MP, Katzenellenbogen BS, Kato S, Hopp T, Fuqua SA, Lopez GN, Kushner PJ, Pestell RG. Direct acetylation of the estrogen receptor alpha hinge region by p300 regulates transactivation and hormone sensitivity. J Biol Chem. 2001 May 25;276(21):18375-83.
- Tazebay UH, Wapnir IL, Levy O, Dohan O, Zuckier LS, Zhao QH, Deng HF, Amenta PS, Fineberg S, Pestell RG, Carrasco N. The mammary gland iodide transporter is expressed during lactation and in breast cancer. Nat Med. 2000 Aug;6(8):871-8.
- Fu M, Wang C, Reutens AT, Wang J, Angeletti RH, Siconolfi-Baez L, Ogryzko V, Avantaggiati ML, Pestell RG. p300 and p300/cAMP-response element-binding protein-associated factor acetylate the androgen receptor at sites governing hormone-dependent transactivation. J Biol Chem. 2000 Jul 7;275(27):20853-60.
- Albanese C, Reutens AT, Bouzahzah B, Fu M, D''Amico M, Link T, Nicholson R, Depinho RA, Pestell RG. Sustained mammary gland-directed, ponasterone A-inducible expression in transgenic mice. FASEB J. 2000 May;14(7):877-84.
- Lin SY, Xia W, Wang JC, Kwong KY, Spohn B, Wen Y, Pestell RG, Hung MC. Beta-catenin, a novel prognostic marker for breast cancer: its roles in cyclin D1 expression and cancer progression. Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4262-6.
- Lee RJ, Albanese C, Fu M, D''Amico M, Lin B, Watanabe G, Haines GK 3rd, Siegel PM, Hung MC, Yarden Y, Horowitz JM, Muller WJ, Pestell RG. Cyclin D1 is required for transformation by activated Neu and is induced through an E2F-dependent signaling pathway. Mol Cell Biol. 2000 Jan;20(2):672-83.
- Jiao, X., Katiyar, S., Liu, M., Mueller, S., Lisanti, M., Li, A., Pestell, T., Wu, K., Ju, X., Li, Z., Wagner, E., Takeya, T., Wang, C., Pestell, R.G. Disruption of c-jun reduces cellular migration and invasion through inhibition of c-Src and hyperactivation of ROCK II kinase, Mol. Biol. Cell., 2008. 19(4):1378-1390.
- Wu, K., Katiyar, S., Ju, X., Popov, V., Liu, M., Jiao, X., Li, A., Lisanti, M., Casola, A., Pestell, R.G. Dachshund inhibits oncogene-induced breast cancer cellular migration and invasion through suppression of Interleukin-8. Proc. Natl. Acad. Sci. U.S.A. (2008); 105(19); 6924-9.
- Zuoren Yu, Chenguang Wang, Min Wang, Zhiping Li, Mathew Casimiro, Manran Liu, Kongming Wu, James Whittle, Xiaoming Ju, Peter MacCue, Richard G. Pestell. A cyclin D1/miRNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation. (2008). In press.
|
|
Individual Expertise profile of
Richard G Pestell, M.D., Ph.D., Copyright © Richard G Pestell, M.D., Ph.D..
Last Updated
by Admin
: Tuesday, March 3, 2009 5:05:53 PM
|
|
|---|
|
|
|
|
|
 |
|
|
