Lgr4 regulates mammary gland development and stem cell activity through the pluripotency transcription factor Sox2

Female mice heterozygous for a genetic mutation in transcription factor forkhead box p3 (Foxp3) spontaneously develop mammary cancers; however, the underlying mechanism is not well understood. We hypothesised that increased cancer susceptibility is associated with an underlying perturbation in mammary gland development. The role of Foxp3 in mammary ductal morphogenesis was investigated in heterozygous Foxp3Sf/+ and wildtype Foxp3+/+ mice during puberty and at specific stages of the oestrous cycle. No differences in mammary ductal branching morphogenesis, terminal end bud formation or ductal elongation were observed in pubertal Foxp3Sf/+ mice compared with Foxp3+/+ mice. During adulthood, all mice underwent normal regular oestrous cycles. No differences in epithelial branching morphology were detected in mammary glands from mice at the oestrus, metoestrus, dioestrus and pro-oestrus stages of the cycle. Furthermore, abundance of Foxp3 mRNA and protein in the mammary gland and lymph nodes was not altered in Foxp3Sf/+ mice compared with Foxp3+/+ mice. These studies suggest that Foxp3 heterozygosity does not overtly affect mammary gland development during puberty or the oestrous cycle. Further studies are required to dissect the underlying mechanisms of increased mammary cancer susceptibility in Foxp3Sf/+ heterozygous mice and the function of this transcription factor in normal mammary gland development.

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Plasticity and Potency of Mammary Stem Cell Subsets During Mammary Gland Development

International Journal of Molecular Sciences ◽

10.3390/ijms20092357 ◽

2019 ◽

Vol 20 (9) ◽

pp. 2357 ◽

Cited By ~ 1

Author(s):

Eunmi Lee ◽

Raziye Piranlioglu ◽

Max S. Wicha ◽

Hasan Korkaya

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Mammary Gland ◽

Mammary Gland Development ◽

Mammary Epithelial ◽

Stem Cell Markers ◽

Quiescent State ◽

Mammary Stem Cells ◽

Mammary Stem ◽

Gland Development

It is now widely believed that mammary epithelial cell plasticity, an important physiological process during the stages of mammary gland development, is exploited by the malignant cells for their successful disease progression. Normal mammary epithelial cells are heterogeneous and organized in hierarchical fashion, in which the mammary stem cells (MaSC) lie at the apex with regenerative capacity as well as plasticity. Despite the fact that the majority of studies supported the existence of multipotent MaSCs giving rise to both basal and luminal lineages, others proposed lineage restricted unipotent MaSCs. Consistent with the notion, the latest research has suggested that although normal MaSC subsets mainly stay in a quiescent state, they differ in their reconstituting ability, spatial localization, and molecular and epigenetic signatures in response to physiological stimuli within the respective microenvironment during the stages of mammary gland development. In this review, we will focus on current research on the biology of normal mammary stem cells with an emphasis on properties of cellular plasticity, self-renewal and quiescence, as well as the role of the microenvironment in regulating these processes. This will include a discussion of normal breast stem cell heterogeneity, stem cell markers, and lineage tracing studies.

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Early Steps of Mammary Stem Cell Transformation by Exogenous Signals; Effects of Bisphenol Endocrine Disrupting Chemicals and Bone Morphogenetic Proteins

Cancers ◽

10.3390/cancers11091351 ◽

2019 ◽

Vol 11 (9) ◽

pp. 1351 ◽

Cited By ~ 5

Author(s):

Nora Jung ◽

Veronique Maguer-Satta ◽

Boris Guyot

Keyword(s):

Breast Cancer ◽

Stem Cell ◽

Mammary Gland ◽

Bone Morphogenetic Proteins ◽

Mammary Gland Development ◽

Cell Transformation ◽

Current Knowledge ◽

Endocrine Disrupting Chemicals ◽

Normal Mammary Gland ◽

Gland Development

Estrogens are major regulators of the mammary gland development, notably during puberty, via estrogen receptor (ER) activation, leading to the proliferation and differentiation of mammary cells. In addition to estrogens, the bone morphogenetic proteins (BMPs) family is involved in breast stem cell/progenitor commitment. However, these two pathways that synergistically contribute to the biology of the normal mammary gland have also been described to initiate and/or promote breast cancer development. In addition to intrinsic events, lifestyle habits and exposure to environmental cues are key risk factors for cancer in general, and especially for breast cancer. In the latter case, bisphenol A (BPA), an estrogen-mimetic compound, is a critical pollutant both in terms of the quantities released in our environment and of its known and speculated effects on mammary gland biology. In this review, we summarize the current knowledge on the actions of BMPs and estrogens in both normal mammary gland development and breast cancer initiation, dissemination, and resistance to treatment, focusing on the dysregulations of these processes by BPA but also by other bisphenols, including BPS and BPF, initially considered as safer alternatives to BPA.

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