From milk to malignancy: the role of mammary stem cells in development, pregnancy and breast cancer.
Adult stem cells of the mammary gland (MaSCs) are a highly dynamic population of cells that are responsible for the generation of the gland during puberty and its expansion during pregnancy. In recent years significant advances have been made in understanding how these cells are regulated during these developmentally important processes both in humans and in mice. Understanding how MaSCs are regulated is becoming a particularly important area of research, given that they may be particularly susceptible targets for transformation in breast cancer. Here, we summarize the identification of MaSCs, how they are regulated and the evidence for their serving as the origins of breast cancer. In particular, we focus on how changes in MaSC populations may explain both the increased risk of developing aggressive ER/PR(-) breast cancer shortly after pregnancy and the long-term decreased risk of developing ER/PR(+) tumors.
Department of Molecular Biology, Princeton University, Washington Road, Princeton, NJ 08544, USA.
Benjamin
B
Tiede
Yibin
Y
Kang
D000818:Animals; D001943:Breast Neoplasms / Q000209:etiology* / Q000517:prevention & control; D005260:Female; D006801:Humans; D008321:Mammary Glands, Animal / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D042361:Mammary Glands, Human / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D008895:Milk, Human / Q000502:physiology*; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
Dev Biol. 2009 May 15;329(2):227-41
19269284
Cell Res. 2007 Jan;17(1):3-14
17179981
Cell. 2000 Sep 29;103(1):41-50
11051546
Cell. 2008 May 16;133(4):704-15
18485877
Cancer Res. 2008 Jun 15;68(12):4674-82
18559513
J Biol Chem. 2004 Nov 26;279(48):50069-77
15361520
Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2196-201
16452162
Cancer Res. 1996 Jan 15;56(2):402-4
8542598
Breast Cancer Res. 2010;12(2):R21
20346151
Genes Dev. 1995 Oct 1;9(19):2364-72
7557388
Nat Med. 2008 Dec;14(12):1384-9
19029987
Genes Dev. 2004 Jan 15;18(2):126-31
14729569
Stem Cells. 2008 Feb;26(2):364-71
17975224
Mol Endocrinol. 2000 Mar;14(3):359-68
10707954
Dev Biol. 2007 Mar 1;303(1):29-44
17222404
Int J Cancer. 1983 Jun 15;31(6):701-4
6862681
Cancer Res. 2008 Feb 15;68(4):989-97
18281472
Breast Cancer Res. 2009;11(2):R20
19386118
Dev Biol. 1997 Apr 15;184(2):385-401
9133444
Genes Dev. 2010 Sep 1;24(17):1882-92
20810647
Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8
12629218
Nature. 2001 Jun 28;411(6841):1017-21
11429595
Breast Cancer Res Treat. 1996;38(3):305-11
8739084
Nature. 2010 Jun 10;465(7299):798-802
20383121
Br J Cancer. 2005 Jan 17;92(1):167-75
15597097
Genes Dev. 2008 Mar 15;22(6):711-21
18347089
Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):2989-94
20133621
Cell Stem Cell. 2010 Jun 4;6(6):568-77
20569694
Cell Death Differ. 2010 Oct;17(10):1600-12
20379195
Nat Genet. 1995 Sep;11(1):17-26
7550308
PLoS One. 2009 Aug 12;4(8):e6594
19672307
Stem Cells. 2011 Jan;29(1):119-27
21280161
Stem Cells. 2008 Dec;26(12):3205-9
18787212
Nature. 2000 Aug 17;406(6797):747-52
10963602
Science. 2002 May 10;296(5570):1046-9
12004111
Nat Med. 1997 Jul;3(7):730-7
9212098
Dev Biol. 2008 Jan 1;313(1):130-41
17996864
Am J Epidemiol. 1994 Apr 15;139(8):819-35
8178795
Nature. 2006 Feb 23;439(7079):993-7
16395311
J Natl Cancer Inst. 2006 Jul 19;98(14):1011-4
16849684
Cell. 2007 May 4;129(3):523-36
17482546
Nat Med. 2009 Aug;15(8):907-13
19648928
Cell. 2009 Aug 7;138(3):592-603
19665978
Breast Dis. 2007;28:63-8
18057544
Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5076-81
9560231
Cell Stem Cell. 2008 Oct 9;3(4):429-41
18940734
Development. 1998 May;125(10):1921-30
9550724
Nat Cell Biol. 2008 Jun;10(6):716-22
18469806
Stem Cells. 2008 May;26(5):1253-64
18292212
Cold Spring Harb Perspect Biol. 2011 Feb 01;3(2):
20926515
Cell. 2010 Jan 8;140(1):62-73
20074520
Cell. 2006 Mar 24;124(6):1111-5
16564000
Cancer Cell. 2010 Jan 19;17(1):65-76
20129248
Am J Pathol. 2010 Jun;176(6):2911-20
20395444
J Mammary Gland Biol Neoplasia. 2007 Sep;12(2-3):153-62
17566854
Cancer Res. 2007 Sep 15;67(18):8671-81
17875707
Cancer Res. 2008 Oct 1;68(19):7711-7
18829523
Cell. 2009 Sep 18;138(6):1083-95
19766563
J Cell Sci. 1988 May;90 ( Pt 1):173-83
3198708
Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1680-5
18230721
Dev Biol. 2006 May 15;293(2):565-80
16581056
Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10567-70
12149477
Cancer. 1989 Jul 1;64(1):196-202
2731116
Breast Cancer Res Treat. 1992;23(3):211-8
1463860
Trends Mol Med. 2010 Mar;16(3):145-51
20149745
Oncogene. 2004 Sep 9;23(41):6980-5
15286714
Development. 2005 Feb;132(4):681-7
15647322
Dev Biol. 1999 Jun 1;210(1):96-106
10364430
Nature. 2007 Oct 25;449(7165):1003-7
17934449
Genes Dev. 2008 Mar 1;22(5):581-6
18316476
Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10869-74
11553815
Cancer Res. 2009 May 15;69(10):4116-24
19435916
PLoS One. 2009 Nov 25;4(11):e8035
19946375
Cancer Res. 1959 Jun;19(5):515-20
13663040
Radiat Res. 2003 Dec;160(6):707-17
14640793
Breast Cancer Res Treat. 2008 Oct;111(3):439-48
17990101
J Natl Cancer Inst. 1974 Sep;53(3):609-14
4369771
Genes Dev. 2009 Oct 15;23(20):2382-7
19833766
Epidemiol Rev. 1993;15(1):36-47
8405211
Radiat Res. 1994 May;138(2):209-23
8183991
J Natl Cancer Inst. 1983 Jun;70(6):1027-31
6574271
Development. 2002 Mar;129(6):1377-86
11880347
Endocr Relat Cancer. 2007 Dec;14(4):907-33
18045947
Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15852-7
17890319
Stem Cells. 2010 Mar 31;28(3):535-44
20054865
Nature. 2006 Jan 5;439(7072):84-8
16397499
Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15449-54
20713713
Cell. 2001 Dec 14;107(6):763-75
11747812
Development. 2008 Mar;135(6):995-1003
18296651
Virchows Arch. 2005 Oct;447(4):688-94
16012853
Cancer Cell. 2007 Dec;12(6):542-58
18068631
J Mammary Gland Biol Neoplasia. 2010 Jun;15(2):117-34
20490631
Breast Cancer Res. 2005;7(3):131-42
15987443
Genes Dev. 2003 May 15;17(10):1253-70
12756227
Nat Cell Biol. 2007 Feb;9(2):201-9
17187062
Microsc Res Tech. 2001 Jan 15;52(2):155-62
11169863
Br J Cancer. 1997;75(1):116-23
9000608
Cancer. 1997 Mar 15;79(6):1203-10
9070499
J Cell Sci. 2002 Jun 1;115(Pt 11):2381-8
12006622
Int J Surg Pathol. 2003 Apr;11(2):65-74
12754622
Cell. 1995 Aug 25;82(4):621-30
7664341
Int J Biol Sci. 2008 May 04;4(3):133-42
18461147
Breast Cancer Res. 2006;8(4):R49
16882347
Mol Endocrinol. 2002 Sep;16(9):2034-51
12198241