Alveolar progenitor cells develop in mouse mammary glands independent of pregnancy and lactation.
We have previously described pluripotent, parity-induced mammary epithelial cells (PI-MEC) marked by Rosa26-lacZ expression in the mammary glands of parous females. PI-MEC act as lobule-limited epithelial stem/progenitor cells. To determine whether parity is necessary to generate PI-MEC, we incubated mammary explant cultures from virgin mice in vitro with insulin alone (I), hydrocortisone alone (H), prolactin alone (Prl), or a combination of these lactogenic hormones (IHPrl). Insulin alone activated the WAP-Cre gene. Hydrocortisone and prolactin alone did not. Any combination of hormones that included insulin was effective. Only I, H and Prl together were able to induce secretory differentiation and milk protein synthesis. In addition, EGF, IGF-2 and IGF-1 added individually produced activated (lacZ(+)) PI-MEC in explant cultures. Neither estrogen nor progesterone induced WAP-Cre expression in the explants. None of these positive initiators of WAP-Cre expression in PI-MEC were effective in mammospheres or two-dimensional cultures of mammary epithelium, indicating the indispensability of epithelial-stromal interaction in PI-MEC activation. Like PI-MEC, lacZ(+) cells from virgin explants proliferated and contributed progeny to mammospheres in vitro and to epithelial outgrowths in vivo after transplantation. LacZ(+) cells induced in virgin mouse mammary explants were multipotent (like PI-MEC) in impregnated hosts producing lacZ(+) mammary alveolar structures comprised of both myoepithelial and luminal progeny. These data demonstrate PI-MEC, a mammary epithelial sub-population of lobule-limited progenitor cells, are present in nulliparous female mice before parity and, like the PI-MEC observed following parity, are capable of proliferation, self-renewal and the capacity to produce progeny of diverse epithelial cell fates.
Booth
Brian W
BW
Mammary Biology and Tumorigenesis Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Boulanger
Corinne A
CA
Smith
Gilbert H
GH
D000818:Animals; D002450:Cell Communication; D002454:Cell Differentiation; D049109:Cell Proliferation; D004815:Epidermal Growth Factor / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology* / Q000637:transplantation; D005260:Female; D006854:Hydrocortisone / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D019426:Integrases / Q000235:genetics; D007763:Lac Operon; D007774:Lactation; D008321:Mammary Glands, Animal / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D008894:Milk Proteins / Q000096:biosynthesis / Q000235:genetics; D010298:Parity; D039904:Pluripotent Stem Cells / Q000378:metabolism / Q000502:physiology*; D011247:Pregnancy; D011388:Prolactin / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics; D022661:RNA, Untranslated; D015398:Signal Transduction; D018874:Spheroids, Cellular; D033581:Stem Cell Transplantation; D017154:Stromal Cells / Q000378:metabolism / Q000502:physiology; D013997:Time Factors; D046509:Tissue Culture Techniques
C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D007328:Insulin; D008894:Milk Proteins; D011506:Proteins; D022661:RNA, Untranslated; C024471:whey acidic proteins; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D011388:Prolactin; C045073:Cre recombinase; D019426:Integrases; D006854:Hydrocortisone