Journal
JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA
Volume 10, Issue 1, Pages 25-36Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10911-005-2538-1
Keywords
mammary gland; differentiation; parity-induced mammary epithelial cells; stem cells; Cre recombinase; tumorigenesis; ErbB2; MMTV
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Funding
- NATIONAL CANCER INSTITUTE [Z01BC010021, R01CA093797] Funding Source: NIH RePORTER
- NCI NIH HHS [CA93797] Funding Source: Medline
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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 females 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.
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