Pregnancy and stem cell behavior.
The identification of cancer-initiating epithelial subtypes (i.e. cancer stem cells) is important for gaining a more comprehensive understanding of the process of neoplastic transformation and tumorigenesis. Since reproductive history has a major impact on breast tumorigenesis, it is reasonable to assume that pregnancy and lactation have enduring effects on the cancer susceptibility of multipotent progenitors. Using the Cre-lox technology as a tool to genetically label pregnancy-hormone-responsive cells, we identified a mammary epithelial subtype that is abundant in parous females. These pregnancy-induced mammary epithelial cells (PI-MECs) originate from differentiating cells during the first pregnancy and lactation cycle. They do not undergo apoptosis during postlactational remodeling, and they persist throughout the remainder of a female's life. In this review, we discuss the biological relevance of PI-MECs in multiparous females and their important stem cell-like features, such as self renewal, as well as their ability to produce progeny with diverse cellular fates. Using appropriate animal models, we further demonstrate that PI-MECs are cellular targets for pregnancy-enhanced mammary tumorigenesis.
Wagner
Kay-Uwe
KU
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Nebraska Medical Center, Omaha, Nebraska 68198, USA. kuwagner@unmc.edu
Smith
Gilbert H
GH
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007774:Lactation / Q000502:physiology; D010298:Parity / Q000502:physiology*; D011247:Pregnancy; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000473:pathology*