PER2 regulation of mammary gland development

Development
Cole M McQueenWeston W Porter

Abstract

The molecular clock plays key roles in daily physiological functions, development and cancer. Period 2 (PER2) is a repressive element, which inhibits transcription activated by positive clock elements, resulting in diurnal cycling of genes. However, there are gaps in our understanding of the role of the clock in normal development outside of its time-keeping function. Here, we show that PER2 has a noncircadian function that is crucial to mammalian mammary gland development. Virgin Per2-deficient mice, Per2-/- , have underdeveloped glands, containing fewer bifurcations and terminal ducts than glands of wild-type mice. Using a transplantation model, we show that these changes are intrinsic to the gland and further identify changes in cell fate commitment. Per2-/- mouse mammary glands have a dual luminal/basal phenotypic character in cells of the ductal epithelium. We identified colocalization of E-cadherin and keratin 14 in luminal cells. Similar results were demonstrated using MCF10A and shPER2 MCF10A human cell lines. Collectively this study reveals a crucial noncircadian function of PER2 in mammalian mammary gland development, validates the Per2-/- model, and describes a potential role for PER2 in breast cancer.

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Citations

Jan 28, 2020·Autophagy·Jessica ElswoodWeston W Porter
Jul 7, 2020·Frontiers in Endocrinology·Sneha SundaramLin Yan
Feb 6, 2020·International Journal of Molecular Sciences·Xiaoyue PanSamantha Mota
Oct 7, 2020·Annual Review of Cell and Developmental Biology·Joseph Lewis BedontAmita Sehgal
Oct 22, 2020·Seminars in Cell & Developmental Biology·Priscila Ferreira SlepickaCamila O Dos Santos
Aug 17, 2020·Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms·Udita BagchiArthur A Bergen
May 19, 2021·Médecine sciences : M/S·Eva Hadadi, Hervé Acloque
May 21, 2021·International Journal of Oral Science·Wushuang HuangYaling Song

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