The concept of stem cell in the mammary gland and its implication in morphogenesis, cancer and prevention.
The breast attains its maximum development during pregnancy and lactation. After menopause the breast regresses in both nulliparous and parous women containing lobular structures that have been designated lobules type 1. Despite the similarity in the lobular composition of the breast at menopause, the fact that nulliparous women are at higher risk of developing breast cancer than parous women, indicates that Lobules type 1 in these two groups of women might be biologically different, or exhibit different susceptibility to carcinogenesis. Based on these observations it was postulated that the Lobule type 1 found in the breast of nulliparous women and of parous women with breast cancer never went through the process of differentiation, retaining a high concentration of epithelial cells that are targets for carcinogens and therefore susceptible to undergo neoplastic transformation, these cell are called Stem cells 1, whereas Lobules type 1 structures found in the breast of early parous postmenopausal women free of mammary pathology, on the other hand, are composed of an epithelial cell population that is refractory to transformation called Stem cells 2. It was further postulated that the degree of differentiation acquired through early pregnancy has changed the "genomic signature" that differentiates the Lobule type 1 from the early parous women from that of the nulliparous women by shifting the Stem cell 1 to a Stem cell 2 that is refractory to carcinogenesis, making this the postulated mechanism of protection conferred by early full term pregnancy. The identification of a putative breast stem cell (Stem cell 1) has reached in the last decade a significant impulse and several markers also reported for other tissues have been found in the mammary epithelial cells of both rodents and humans. Although still more work needs to be done in order to better understand the role of the Stem cell 2 and its interaction with the genes that confer it a specific signature, collectively, the data presently available provides evidence that pregnancy, through the process of cell differentiation, shifts the Stem cell 1 to Stem cell 2, cells that exhibit a specific genomic signature that could be responsible for the refractoriness of the mammary gland to carcinogenesis.
Russo
Jose
J
Breast Cancer Research Laboratory, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. J_russo@fccc.edu
Balogh
Gabriela A
GA
Chen
Jinqiang
J
Fernandez
Sandra V
SV
Fernbaugh
Rachael
R
Heulings
Rebecca
R
Mailo
Daniel A
DA
Moral
Raquel
R
Russo
Patricia A
PA
Sheriff
Fathima
F
Vanegas
Johana E
JE
Wang
Richard
R
Russo
Irma H
IH
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D004847:Epithelial Cells / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D047629:Estrogen Receptor beta / Q000096:biosynthesis; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008321:Mammary Glands, Animal / Q000473:pathology*; D042361:Mammary Glands, Human / Q000473:pathology*; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism*; D011247:Pregnancy; D012313:RNA; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism*; D013997:Time Factors
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012313:RNA