Results Of Transgenic Mouse Study Directly Applicable To Human Breast Cancer Tumor Study

Main Category: Breast Cancer
Also Included In: Biology / Biochemistry;  Genetics
Article Date: 26 Oct 2009 - 1:00 PDT

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Sanford Barsky, M.D., who holds faculty positions at the University of Nevada School of Medicine as chair of the pathology department and Nevada Cancer Institute chief of pathology, is part of a team that has a paper on transgenic mouse mammary tumors with direct relevance to human breast cancer published in the October 22 issue of the scientific journal Nature.

The article, "Pten in stromal fibroblasts suppresses mammary epithelial tumours," shows that a key signaling pathway that operates in mammary gland connective tissue cells helps to suppress the development of mammary tumors. This study is important because it helps tease apart the complex links between tumor microenvironment and cancer development.

It had been thought that the connective tissue surrounding tumors - also known as the tumor microenvironment - is important for helping the tumor to grow and survive, but it was not clear just how. This study revealed that deletion of the tumour suppressor gene Pten in fibroblasts - connective tissue cells - of mammary glands leads to the accelerated development of mammary tumors in mice. Furthermore, tumor development goes hand-in-hand with other changes in the local cellular environment, such as increased blood vessel formation and immune cell infiltration.

Pten loss and related changes in gene expression can also be observed in the connective tissue of breast cancers in women, suggesting that the signalling system operates in humans as well as mice. The team also highlights Pten's influence on a transcription factor called Ets2 as being critical for Pten's tumour suppressive functions in the connective tissue.

Barsky, who serves as chief of pathology for Nevada Cancer Institute in Las Vegas and vice president, academic liaison to University of Nevada, Reno, is also professor and chair of the Department of Pathology of the University of Nevada School of Medicine. He joined both the School of Medicine and the Nevada Cancer Institute in September 2009.

Barsky, who has a strong research and clinical background, has published more than 150 peer reviewed articles and more than 200 abstracts.

Pten in stromal fibroblasts suppresses mammary epithelial tumours
Anthony J. Trimboli 1,2*, Carmen Z. Cantemir-Stone 3*, Fu Li1, 3*, Julie A. Wallace 3, Anand Merchant 3, Nicholas Creasap 1,2, John C. Thompson 1,2, Enrico Caserta 1,2, Hui Wang 1,2, Jean-Leon Chong 1,2, Shan Naidu 1,2,4, Guo Wei 1,3, Sudarshana M. Sharma 3, Julie A. Stephens 5, Soledad A. Fernandez 5, Metin N. Gurcan 6, Michael B. Weinstein 1,2, Sanford H. Barsky 7{, Lisa Yee8, Thomas J. Roso l4, Paul C. Stromberg 4, Michael L. Robinson9 {, Francois Pepin 10,11, Michael Hallett 10,11, Morag Park 10,12, Michael C. Ostrowski 3,13 & Gustavo Leone 1,2,13
1Department of Molecular Genetics, College of Biological Sciences,
2Department of Molecular Virology, Immunology and Medical Genetics,
3Department of Molecular and Cellular Biochemistry, College of Medicine,
4Department of Veterinary Biosciences, College of Veterinary Medicine,
5Center for Biostatistics, Office of Health Sciences,
6Department of Biomedical Informatics,
7Department of Pathology and
8Department of Surgery, School of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
9Center for Molecular and Human Genetics, Columbus Children's Research Institute, Columbus, Ohio 43205, USA.
10Department of Biochemistry, Rosalind and Morris Goodman Cancer Center,
11McGill Center for Bioinformatics,
12Department of Oncology, McGill University, Que´bec H3A 1A1, Canada.
13Tumor Microenvironment Program, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA. {Present addresses: Department of Pathology, University of Nevada School of Medicine, Reno, Nevada 89557, and Nevada Cancer Institute, Las Vegas, Nevada 89135, USA (S.H.B.); Department of Zoology, Miami University, Oxford, Ohio 45056, USA (M.L.R.).
*These authors contributed equally to this work.

Source:
Anne McMillin
University of Nevada, Reno