Richard G. Pestell, M.D., Ph.D.


Director, Sidney Kimmel Cancer Center,
Chairman, Cancer Biology,
Associate Dean, Cancer Programs (JMC),
Vice President, Oncology Services (TJUH)

Professor
Cancer Biology

Molecular mechanisms and gene therapy of breast and prostate cancer.

Telephone
215-503-5692
(215) 503-9334 FAX

Office Address
1050 BLSB
233 S. 10th Street
Philadelphia, PA 19107

Email Address
Richard.Pestell@jefferson.edu

Further Information
Office of the Director

 

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
 

PubMed Link For Pestell RG


Selected Publications

Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C, Darnell JE. Stat3 as an oncogene. Cell. 98(3):295-303, 1999. ( Abstract )

Fan S, Wang J, Yuan R, Ma Y, Meng Q, Erdos MR, Pestell RG, Yuan F, Auborn KJ, Goldberg ID, Rosen EM. BRCA1 inhibition of estrogen receptor signaling in transfected cells. Science. 284(5418):1354-6, 1999. ( Abstract )

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. 6(8):871-8, 2000. ( Abstract )

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. 9(5):1017-29, 2002. ( Abstract )

Huang E, Ishida S, Pittman J, Dressman H, Bild A, Kloos M, D'Amico M, Pestell RG, West M, Nevins JR. Gene expression phenotypic models that predict the activity of oncogenic pathways. Nat Genet. 34(2):226-30, 2003. ( Abstract )

Genander M, Halford MM, Xu NJ, Eriksson M, Yu Z, Qiu Z, Martling A, Greicius G, Thakar S, Catchpole T, Chumley MJ, Zdunek S, Wang C, Holm T, Goff SP, Pettersson S, Pestell RG, Henkemeyer M, Frisen J. Dissociation of EphB2 signaling pathways mediating progenitor cell proliferation and tumor suppression. Cell. 139(4):679-92, 2009. ( Abstract )
 

Web page revised: September 17, 2014.
URL: http://www.kcc.tju.edu/kcc/kccnew/staff/staffdefault.php


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