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Hormone Molecular Biology and Clinical Investigation

Editor-in-Chief: Pasqualini, Jorge R.

Editorial Board Member: Fujimoto, Jiro / Hubalek, Michael / Morfin, Robert / Saad, Farid / Schally, Andrew V. / Alexis, Michael N. / Baniahmad, Aria / Beato, Miguel / Bouillon, Roger / Bouvier, Michel / Brodie, Angela / Campagnoli, Carlo / Carruba, Giuseppe / Catt, FRACP, Kevin J. / Chen, Shiuan / Chetrite, Gerard / Cidlowski, John A. / Clarke, Robert / Coelingh Bennink, Herjan J.T. / Danza, Giovanna / Darbre, Philippa D. / Daxenbichler, Günter / Kloet, Ronald / Nicola, Alejandro F. / Drouin, Jacques / Dufau, Maria L. / Edwards, Dean P. / Evans, Dean / Falany, Charles N. / Fernandez-Perez, Leandro / Ferroud, Clotilde / Flores-Morales, Amilcar / Garcia-Segura, Luis M. / Gee, J.M.W. / Genazzani, Andrea R. / Greene, Geoffrey L. / Groner, Bernd / Hilakivi-Clarke, Leena / Hampl, Richard / Iwase, Hirotaka / Jordan, V.Craig / Klocker, Helmut / Kurebayashi, Jyunichi / Labrie, Fernand / Lee, Adrian V. / Libertun, Carlos / Luu-The, Van / Mendelson, Carole R. / Mück, Alfred O. / Murphy, Leigh C. / Muti, Paola / Nicholson, Robert / Norman, Anthony W. / O'Malley, Bert W. / Rafestin-Oblin, Marie-Edith / Raynaud, Jean-Pierre / Renoir, Michel / Sanchez, Edwin R. / Schindler, Adolf E. / Senn, Hans-Jörg / Söderqvist, Gunnar / Speirs, Valerie / Stanczyk, Frank Z. / Starka, Luboslav / Sutherland, Robert / Sutter, Thomas R. / Traish, Adbulmaged / Verhoeven, Guido / Wahli, Walter / Wildt, Ludwig / Yang, Kaiping / Ylikomi, Timo

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Estrogen-induced breast cancer is the result of disruption of asymmetric cell division of the stem cell

Jose Russo1 / Kara Snider1 / Julia S. Pereira1 / Irma H. Russo1

1Breast Cancer Research Laboratory, Fox Chase Cancer Center, Philadelphia, PA, USA

Corresponding author: Jose Russo, MD, Professor, Breast Cancer Research Laboratory, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA Phone: +1-215-728-4782, Fax: +1-215-728-2180,

Citation Information: Hormone Molecular Biology and Clinical Investigation. Volume 1, Issue 2, Pages 53–65, ISSN (Online) 1868-1891, ISSN (Print) 1868-1883, DOI: 10.1515/HMBCI.2010.011, September 2009

Publication History

Received:
2009-07-15
Accepted:
2009-08-19
Published Online:
2009-09-17

Abstract

Stem cells have the unique potential to divide asymmetrically to generate daughters with distinct fates, one which remains a stem cell and the other which turns into a cell committed to differentiation. By dividing asymmetrically, stem cells maintain the stem cell pool and simultaneously generate committed cells that reconstitute the organ, for example, to prepare the breast for a new pregnancy after involution from a previous pregnancy and lactation process. In addition to the in vivo models of mammary morphogenesis, there are in vitro systems that make the ductulogenic pattern of breast epithelia growth more amenable to study in critically determined conditions. The human breast epithelial cells MCF-10F formed tubules when grown in type I collagen and we demonstrated that treatment of these cells with 17β-estradiol (E2) induces phenotypical changes indicative of neoplastic transformation. The transformation of MCF-10F by E2 is associated with impaired ductal morphogenesis caused by an alteration of the stem cells unique potential to divide asymmetrically, inducing formation of solid masses and mimicking intraductal carcinoma that progresses into an invasive and tumorigenic phenotype. In the present work, we present evidence for the mechanism of cell asymmetry which leads to normal ductulogenesis and show how the normal stem cell is transformed into a cancer stem cell by altering this process. Furthermore, we demonstrate that the carcinogenic agent, in this case E2, induces a defect in the asymmetric cell division program of the normal mammary stem cell.

Keywords: asymmetric cell division; breast cancer; carcinogenesis; estrogen; stem cell

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