Estrogen induced breast cancer is the result in the disruption of the asymmetric cell division of the stem cell.
There is evidence that in the human breast there is a stem cell population that can give rise to many different cell types and have the unique potential to divide asymmetrically. In this way stem cells maintain the stem cell pool and simultaneously generate committed cells that reconstitute the organ for example for preparing the breast for a new pregnancy after the involution from a previous pregnancy and lactation process. In addition to the in vivo models of mammary morphogenesis there are in vitro systems that are more amenable to study in critically determined conditions the ductulogenic pattern of growth of the breast epithelia. Primary mammary epithelial cells grown in collagen matrix are able to form tree-like structures resembling in vivo ductulogenesis. 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 (E(2)) induces phonotypical changes indicative of neoplastic transformation. The transformation of MCF-10F by E(2) is associated with impaired ductal morphogenesis by altering the stem cells unique potential to divide asymmetrically inducing formation of solid masses mimicking intraductal carcinoma that progress to invasive and tumorigenic phenotype. In the present work we present evidence for the mechanism of cell asymmetry leading to normal ductulogenesis and how the normal stem cell is transformed to cancer stem cell by altering this process. Furthermore, we demonstrate that the carcinogenic agent, in this case E(2), induces a defect in the asymmetric cell division program of the normal mammary stem cell.
Breast Cancer Research laboratory, Fox Chase Cancer Center, Philadelphia, PA, USA.
Jose
J
Russo
Kara
K
Snider
Julia S
JS
Pereira
Irma H
IH
Russo
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