title: Fibulin-2 is involved in early extracellular matrix development of the outgrowing mouse mammary epithelium.
abstract: Cell-matrix interactions control outgrowth of mammary epithelium during puberty and pregnancy. We demonstrate here that the glycoprotein fibulin-2 (FBLN2) is strongly associated with pubertal and early pregnant mouse mammary epithelial outgrowth. FBLN2 was specifically localized to the cap cells of the terminal end buds during puberty and to myoepithelial cells during very early pregnancy (days 2-3) even before morphological changes to the epithelium become microscopically visible, but was down-regulated thereafter. Exposure to exogenous oestrogen (E2) or E2 plus progesterone (P) increased Fbln2 mRNA expression in the pubertal gland, indicating hormonal control. FBLN2 was co-expressed and co-localised with the proteoglycan versican (VCAN) and co-localised with laminin (LN), while over-expression of FBLN2 in HC-11 cells increased cell adhesion to several extracellular matrix proteins including LN and fibronectin, but not collagens. Mammary glands from Fbln2 knockout mice showed no obvious phenotype but increased fibulin-1 (FBLN1) staining was detected, suggesting a compensatory mechanism by other fibulin family members. We hypothesise that similar to embryonic aortic smooth muscle development, FBLN2 and VCAN expression alters the cell-matrix interaction to allow mammary ductal outgrowth and development during puberty and to enable epithelial budding during pregnancy.
authors: Institute of Cancer Sciences, College of MVLS, University of Glasgow, Glasgow, G12 8QQ, UK.
authors: D
authors: D
authors: Olijnyk
authors: A M
authors: AM
authors: Ibrahim
authors: R K
authors: RK
authors: Ferrier
authors: T
authors: T
authors: Tsuda
authors: M-L
authors: ML
authors: Chu
authors: B A
authors: BA
authors: Gusterson
authors: T
authors: T
authors: Stein
authors: J S
authors: JS
authors: Morris
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004967:Estrogens / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D007797:Laminin / Q000032:analysis / Q000378:metabolism; D008297:Male; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D053675:Versicans / Q000032:analysis / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D004967:Estrogens; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007797:Laminin; D012333:RNA, Messenger; C060820:fibulin; C084612:fibulin 2; D053675:Versicans; D011374:Progesterone