A mammary stem cell population identified and characterized in late embryogenesis reveals similarities to human breast cancer.
Gene expression signatures relating mammary stem cell populations to breast cancers have focused on adult tissue. Here, we identify, isolate, and characterize the fetal mammary stem cell (fMaSC) state since the invasive and proliferative processes of mammogenesis resemble phases of cancer progression. fMaSC frequency peaks late in embryogenesis, enabling more extensive stem cell purification than achieved with adult tissue. fMaSCs are self-renewing, multipotent, and coexpress multiple mammary lineage markers. Gene expression, transplantation, and in vitro analyses reveal putative autocrine and paracrine regulatory mechanisms, including ErbB and FGF signaling pathways impinging on fMaSC growth. Expression profiles from fMaSCs and associated stroma exhibit significant similarities to basal-like and Her2+ intrinsic breast cancer subtypes. Our results reveal links between development and cancer and provide resources to identify new candidates for diagnosis, prognosis, and therapy.
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Benjamin T
BT
Spike
Dannielle D
DD
Engle
Jennifer C
JC
Lin
Samantha K
SK
Cheung
Justin
J
La
Geoffrey M
GM
Wahl
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002280:Basal Cell Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D042361:Mammary Glands, Human / Q000196:embryology* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D018739:Oncogene Proteins v-erbB / Q000235:genetics / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000378:metabolism / Q000473:pathology*; D033581:Stem Cell Transplantation
D018739:Oncogene Proteins v-erbB; D005346:Fibroblast Growth Factors