Runx2 contributes to the regenerative potential of the mammary epithelium.
Although best known for its role in bone development and associated structures the transcription factor RUNX2 is expressed in a wide range of lineages, including those of the mammary gland. Previous studies have indicated that Runx2 can regulate aspects of mammary cell function and influence the properties of cancer cells. In this study we investigate the role of Runx2 in the mammary stem/progenitor population and its relationship with WNT signalling. Results show that RUNX2 protein is differentially expressed throughout embryonic and adult development of the murine mammary gland with high levels of expression in mammary stem-cell enriched cultures. Importantly, functional analysis reveals a role for Runx2 in mammary stem/progenitor cell function in in vitro and in vivo regenerative assays. Furthermore, RUNX2 appears to be associated with WNT signalling in the mammary epithelium and is specifically upregulated in mouse models of WNT-driven breast cancer. Overall our studies reveal a novel function for Runx2 in regulating mammary epithelial cell regenerative potential, possibly acting as a downstream target of WNT signalling.
Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow, G61 1BD.
Nicola
N
Ferrari
Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow, G61 1BD.
Alessandra I
AI
Riggio
Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow, G61 1BD.
Susan
S
Mason
Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow, G61 1BD.
Laura
L
McDonald
Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow, G61 1BD.
Ayala
A
King
Cancer Research UK London Research Institute, Lincoln's Inn Fields, London, WC2A 3LY.
Theresa
T
Higgins
Clare Hall Laboratories, South Mimms, Hertfordshire, EN6 3LD.
Ian
I
Rosewell
University of Glasgow, Garscube Estate, Bearsden, Glasgow, G61 1QH.
James C
JC
Neil
European Cancer Stem Cell Research Institute, Cardiff University, Cardiff, CF24 4HQ.
Matthew J
MJ
Smalley
Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow, G61 1BD.
Owen J
OJ
Sansom
University of Glasgow, Garscube Estate, Bearsden, Glasgow, G61 1QH.
Joanna
J
Morris
University of Glasgow, Garscube Estate, Bearsden, Glasgow, G61 1QH.
Ewan R
ER
Cameron
Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow, G61 1BD.
Karen
K
Blyth
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis*; D004848:Epithelium / Q000254:growth & development* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008321:Mammary Glands, Animal / Q000254:growth & development / Q000378:metabolism*; D051379:Mice; D013234:Stem Cells / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000235:genetics
D050659:Core Binding Factor Alpha 1 Subunit; C493716:Runx2 protein, mouse