Journal
JOURNAL OF CELL BIOLOGY
Volume 162, Issue 6, Pages 1123-1133Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200302090
Keywords
apoptosis; matrix metalloproteinases; stromal-epithelial interaction; terminal end bud; tissue inhibitor of metalloproteinases
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Funding
- NCI NIH HHS [CA58207, CA57621, R01 CA057621, P50 CA058207] Funding Source: Medline
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During puberty, mouse mammary epithelial ducts invade the stromal mammary fat pad in a wave of branching morphogenesis to form a complex ductal tree. Using pharmacologic and genetic approaches, we find that mammary gland branching morphogenesis requires transient matrix metalloproteinase (MMP) activity for invasion and branch point selection. MMP-2, but not MMP-9, facilitates terminal end bud invasion by inhibiting epithelial cell apoptosis at the start of puberty. Unexpectedly, MMP-2 also represses precocious lateral branching during mid-puberty. In contrast, MMP-3 induces secondary and tertiary lateral branching of ducts during mid-puberty and early pregnancy. Nevertheless, the mammary gland is able to develop lactational competence in MMP mutant mice. Thus, specific MMPs refine the mammary branching pattern by distinct mechanisms during mammary gland branching morphogenesis.
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