Cyclin D1 kinase activity is required for the self-renewal of mammary stem and progenitor cells that are targets of MMTV-ErbB2 tumorigenesis.
Transplantation studies have demonstrated the existence of mammary progenitor cells with the ability to self-renew and regenerate a functional mammary gland. Although these progenitors are the likely targets for oncogenic transformation, correlating progenitor populations with certain oncogenic stimuli has been difficult. Cyclin D1 is required for lobuloalveolar development during pregnancy and lactation as well as MMTV-ErbB2- but not MMTV-Wnt1-mediated tumorigenesis. Using a kinase-deficient cyclin D1 mouse, we identified two functional mammary progenitor cell populations, one of which is the target of MMTV-ErbB2. Moreover, cyclin D1 activity is required for the self-renewal and differentiation of mammary progenitors because its abrogation leads to a failure to maintain the mammary epithelial regenerative potential and also results in defects in luminal lineage differentiation.
Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111, USA.
Rinath
R
Jeselsohn
Nelson E
NE
Brown
Lisa
L
Arendt
Ina
I
Klebba
Miaofen G
MG
Hu
Charlotte
C
Kuperwasser
Philip W
PW
Hinds
D000818:Animals; D000957:Antigens, Viral, Tumor / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D019938:Cyclin D1 / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D055879:Gene Knock-In Techniques; D007150:Immunohistochemistry; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000201:enzymology; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism
D000957:Antigens, Viral, Tumor; D019938:Cyclin D1; D018719:Erb-b2 Receptor Tyrosine Kinases; D014758:Viral Core Proteins; C530105:Ccnd1 protein, mouse; C055976:p27 antigen, Mouse mammary tumor virus; C524056:Erbb2 protein, mouse