Loss of Panx1 Impairs Mammary Gland Development at Lactation: Implications for Breast Tumorigenesis.
Pannexin1 (Panx1) subunits oligomerize to form large-pore channels between the intracellular and extracellular milieu that have been shown to regulate proliferation, differentiation and cell death mechanisms. These key cellular responses are ultimately necessary for normal tissue development and function but the role of Panx1 in development, differentiation and function in many tissues remains unexplored, including that of the breast. Panx1 was identified to be expressed in the mammary gland through western blot and immunofluorescent analysis and is dynamically upregulated during pregnancy and lactation. In order to evaluate the role of Panx1 in the context of mammary gland development and function, Panx1-/- mice were evaluated in comparison to wild-type mice in the mammary glands of virgin, lactating and involuting mice. Our results revealed that Panx1 ablation did not affect virgin or involuting mammary glands following histological and whole mount analysis. Panx1 was necessary for timely alveolar development during early lactation based on a decreased number of alveolar lumen following histological analysis and reduced proliferation following Ki67 immunofluorescent labelling. Importantly, the loss of Panx1 in lactating mammary glands did not overtly affect epithelial or secretory differentiation of the mammary gland suggesting that Panx1 is not critical in normal mammary gland function. In addition, PANX1 mRNA expression was correlated with negative clinical outcomes in patients with breast cancer using in silico arrays. Together, our results suggest that Panx1 is necessary for timely alveolar development following the transition from pregnancy to lactation, which may have implications extending to patients with breast cancer.
Department of Physiology and Pharmacology, University of Western Ontario, 1151 Richmond Street, London, Ontario, N6A 5C1, Canada.
Michael K G
MK
Stewart
Centre INRS-Institut Armand-Frappier, 531 Boulevard des Prairies, Laval, Québec, H7V 1B7, Canada.
Isabelle
I
Plante
Department of Anatomy and Cell Biology, University of Western Ontario, 1151 Richmond Street, London, Ontario, N6A 5C1, Canada.
Silvia
S
Penuela
Department of Physiology and Pharmacology, University of Western Ontario, 1151 Richmond Street, London, Ontario, N6A 5C1, Canada.|Department of Anatomy and Cell Biology, University of Western Ontario, 1151 Richmond Street, London, Ontario, N6A 5C1, Canada.
Dale W
DW
Laird
D000818:Animals; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007774:Lactation; D008321:Mammary Glands, Animal / Q000254:growth & development / Q000378:metabolism*; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis
D017630:Connexins; D009419:Nerve Tissue Proteins; C503631:Panx1 protein, mouse