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Hormone-Signaling and Cancer Program

Our central goal is to investigate the role played by pRb2/p130 in breast and prostate cancer formation and progression.

Program Details | Biography Details | Publications

  HORMONE-SIGNALING

  


PROGRAM DETAILS

Over the past several years, our research has been focused on understanding the complex network of signals by which pRb2/p130 regulates cellular proliferation, survival and differentiation, and disclosing the mechanisms responsible for the regulatory disruption of these functions in the neoplastic process. Our central goal is to investigate the role played by pRb2/p130 in breast and prostate cancer formation and progression as well as to understand the interplay between pRb2/p130 and chromatin modifying enzymes in regulating the expression of specific genes involved in the neoplastic process. Specifically, this program focuses on understanding the molecular pathways regulating estrogen and androgen signaling in breast and prostate cancer. Our research hypothesis is that functional alterations of pRb2/p130 represent "hit" events leading to deregulation of hormonal signaling and then uncontrolled cell growth. In this context, we have suggested that the silencing of estrogen receptor alpha (ER-a) gene during breast cancer progression could arise from epigenetic events mediated by pRb2/130 in association with specific enzymes involved in the chromatin remodeling. Furthermore, our work has shown that the epigenetic mechanisms controlled by pRb2/p130 as well as the epigenetic events affecting Rb2/130 gene expression itself, play an important role in the formation and progression of different tumors and can represent key events in the differentiation of human cornea and conjunctiva. Research topics include:

  • Cross-talk betweenpRb family proteins (in particular pRb2/p130) and estrogen receptors (alpha and beta) in prostate and breast cancer formation and progression. Our goal is to develop new protocols for cancer treatment by induction of estrogen receptors expression (estrogen receptor alpha and beta) through the design of new anticancer molecules.

  • Cross-talk between pRb family members and PAI-2 protein during the differentiation of corneal and conjunctiva cells. Our goal is to develop new strategy for the treatment of chronic and acute inflammation of eye and maintenance health vision.

  • Cross-talk between pRb family proteins and chromatin modifying enzymes in lung cancer formation and progression. Our goal is to develop new strategies for lung cancer treatment through gene therapy approaches and design of new anticancer molecules.



 


  HORMONE-SIGNALING

 

BIOGRAPHY DETAILS

Micaela Montanari, Ph.D.
Assistant Professor of Biology
Director, Hormone-Signaling and Cancer Program

email: montanar@temple.edu

Micaela Montanari, Ph.D. is an Assistant Professor of Biology and Director of the Hormone-Signaling and Cancer Program at SHRO. Dr Montanari's research focuses on understanding the molecular mechanisms underlying estrogen/androgen signals alterations in human cells leading to prostate and breast cancer formation and progression. Her work includes investigating the complex network of signals by which pRb family proteins regulate cellular proliferation, survival and differentiation, and to disclose the mechanisms responsible for the regulatory disruption of these functions in the neoplastic process. Dr. Montanari's research has been supported by National Institute of Health (NIH) and several private foundations and organizations.

Research Team:
Marcella Macaluso, PhD, Associate Professor
Francesco Paolo Fiorentino, PhD student
Valentina Caracciolo, Post-Doctoral Fellow
Daniel Burrit, Research Assistant

External Collaborators:
Robert L. Copeland, Jr., Ph.D.
Department of Pharmacology,
College of Medicine
Howard University,
Washington, DC

Christian Bronner, PhD.
Departement de Pharmacologie et Physicochimie
Faculte de Pharmacie
Institut Gilbert-Laustria
Centre National de la Recherche Scientifique
Illkirch, France

Mina Massaro-Giordano, MD.
Scheie Eye Institute
University of Pennsylvania

Christine M. Marshall
Department of Dermatology
University of Pennsylvania
Antonio Russo, MD.
Department of Oncology
University of Palermo
Palermo, Italy

  HORMONE-SIGNALING

 

PUBLICATIONS

Macaluso M., Montanari M *., Noto P.B., Gregorio V., Bronner C. and Giordano A. (2007). Epigenetic modulation of Estrogen Receptor-alpha by pRb Family Proteins: A novel mechanism in breast cancer. Cancer Res, 67(16):7731-7737

Macaluso M, Montanari M and Giordano A. (2006). Rb family proteins as modulators of gene expression and new aspects regarding the interaction with chromatin remodeling enzyme. Oncogene, 25(38): 5263-5267

Montanari M, Macaluso M, Cittadini A and Giordano A. (2006). The role of geminin: from normal control of DNA replication to cancer formation and progression? Cell Death Differ, 13(7): 1052-1056

Macaluso M., Montanari M., Noto P.B., Gregorio V., Surmacz E. and Giordano A. (2006). The regulation of ER-a transcription by pRb2/p130 in breast cancer. Annals Oncol., 17, Suppl 7:vii27-vii29

Macaluso M, Montanari M, Marshall CM , Gambone A, Tosi GM , Giordano A, and Massaro-Giordano M. (2006). Cytoplasmic and nuclear interaction between Rb family proteins and PAI-2: a physiological cross-talk in human cornea and conjunctiva cells. Cell Death Differ, 13(9): 1515-1522

Macaluso M, Montanari M, and Giordano A. (2005). The regulation of ER-a transcription by pRb2/p130 in breast cancer. Annals of Oncology, 16 Suppl 4:iv20-iv22

Macaluso M, Montanari M, Cinti C and Giordano A. (2005). Modulation of cell cycle components byepigenetic and genetic events. Seminars in Oncology, 32(5):452-457

M. Montanari, A. Boninsegna, B. Faraglia, C. Coco, A. Giordano, A. Cittadini and A. Sgambato (2005). Increased expression of geminin stimulates the growth of mammary epithelial cells and is a frequent event in human tumors. J Cell Physiol.; 202(1): 215-222

Sgambato A., Camerini A., Faraglia B., Pavoni E., Montanari M., Spada D., Losasso C., Brancaccio A. and Cittadini A. (2004). Increased Expression of Dystroglycan Inhibits the Growth and Tumorigenicity of Human Mammary Epithelial Cells. Cancer Biol Ther., 3(10): 967-975

R. Puglisi, M. Montanari, P. Chiarella, M. Stefanini and C. Boitani (2004). Regulatory role of BMP-2 and BMP-7 in spermatogonia and Sertoli cell proliferation in the immature mouse. Eur. J. Endocrinol.; 151(4): 511- 520

A. Sgambato, M. Migaldi, M. Montanari, A. Camerini, A. Brancaccio, G. Rossi, R. Cangiano, C. Losasso,G. Capelli, G.P.Trentini and A. Cittadini (2003). Dystroglycan expression is frequently reduced in human breast and colon cancers and is associated with tumor progression. Am. J. Path., vol. 162(3): 849-60

F.I. Wolf, A. Torsello, S. Fasanella, M. Montanari and A. Cittadini (2002). Mechanisms of aging induced by physiologic-like oxidative stress". Biogerontology, vol. 3, suppl.1, 14-15

Wolf F.I., Torsello A., Fasanella S., Covacci V., Montanari M., Boninsegna A. and Cittadini A. (2001). Oxidative DNA damage as a marker of aging in WI-38 human fibroblasts. Exp. Gerontol. 37, 647-656

A. Sgambato, M. Montanari, R. Ardito, B. Faraglia, C. Losasso, B. Giardina, A. Brancaccio, A. Cittadini (2001). Loss of dystroglycan is a frequent event in human primary tumors.Tumori, 87(4)

* Micaela Montanari equally contributed to this article as the first author



 

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