title: Hormone-sensing mammary epithelial progenitors: emerging identity and hormonal regulation.
abstract: The hormone-sensing mammary epithelial cell (HS-MEC-expressing oestrogen receptor-alpha (ERα) and progesterone receptor (PGR)) is often represented as being terminally differentiated and lacking significant progenitor activity after puberty. Therefore while able to profoundly influence the proliferation and function of other MEC populations, HS-MECs are purported not to respond to sex hormone signals by engaging in significant cell proliferation during adulthood. This is a convenient and practical simplification that overshadows the sublime, and potentially critical, phenotypic plasticity found within the adult HS-MEC population. This concept is exemplified by the large proportion (~80 %) of human breast cancers expressing PGR and/or ERα, demonstrating that HS-MECs clearly proliferate in the context of breast cancer. Understanding how HS-MEC proliferation and differentiation is driven could be key to unraveling the mechanisms behind uncontrolled HS-MEC proliferation associated with ERα- and/or PGR-positive breast cancers. Herein we review evidence for the existence of a HS-MEC progenitor and the emerging plasticity of the HS-MEC population in general. This is followed by an analysis of hormones other than oestrogen and progesterone that are able to influence HS-MEC proliferation and differentiation: androgens, prolactin and transforming growth factor-beta1.
authors.affiliation: Dame Roma Mitchell Cancer Research Laboratories (DRMCRL), School of Medicine, Faculty of Health Sciences, The University of Adelaide, Adelaide, SA, 5005, Australia. gerard.tarulli@adelaide.edu.au.
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Tarulli
authors.affiliation: Dame Roma Mitchell Cancer Research Laboratories (DRMCRL), School of Medicine, Faculty of Health Sciences, The University of Adelaide, Adelaide, SA, 5005, Australia.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Laven-Law
authors.affiliation: Breast Cancer Genetics Laboratory, Centre for Personalised Cancer Medicine, School of Medicine, Faculty of Health Sciences, The University of Adelaide, Adelaide, SA, 5005, Australia.
authors.forename: Reshma
authors.initials: R
authors.lastname: Shakya
authors.affiliation: Dame Roma Mitchell Cancer Research Laboratories (DRMCRL), School of Medicine, Faculty of Health Sciences, The University of Adelaide, Adelaide, SA, 5005, Australia.
authors.forename: Wayne D
authors.initials: WD
authors.lastname: Tilley
authors.affiliation: Dame Roma Mitchell Cancer Research Laboratories (DRMCRL), School of Medicine, Faculty of Health Sciences, The University of Adelaide, Adelaide, SA, 5005, Australia.
authors.forename: Theresa E
authors.initials: TE
authors.lastname: Hickey
mesh_terms: D000728:Androgens / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002454:Cell Differentiation; D000066670:Cell Plasticity; D049109:Cell Proliferation; D050657:Core Binding Factor alpha Subunits / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D050990:GATA3 Transcription Factor / Q000378:metabolism; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000378:metabolism; D006801:Humans; D008321:Mammary Glands, Animal / Q000378:metabolism*; D042361:Mammary Glands, Human / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000728:Androgens; D022782:CCAAT-Enhancer-Binding Protein-beta; D050657:Core Binding Factor alpha Subunits; D004268:DNA-Binding Proteins; C116038:ELF5 protein, human; C500759:Elf5 protein, mouse; D047628:Estrogen Receptor alpha; D050990:GATA3 Transcription Factor; D051541:Hepatocyte Nuclear Factor 3-alpha; D050783:Proto-Oncogene Proteins c-ets; D011980:Receptors, Progesterone; D020825:T-Box Domain Proteins; C106884:TBX3 protein, human; C491460:Tbx3 protein, mouse; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D011388:Prolactin
keywords: Androgen; Endocrine hormones; Hormone-sensing cells; Luminal progenitors; Prolactin