title: STAT signaling in mammary gland differentiation, cell survival and tumorigenesis.
abstract: The mammary gland is a unique organ that undergoes extensive and profound changes during puberty, menstruation, pregnancy, lactation and involution. The changes that take place during puberty involve large-scale proliferation and invasion of the fat-pad. During pregnancy and lactation, the mammary cells are exposed to signaling pathways that inhibit apoptosis, induce proliferation and invoke terminal differentiation. Finally, during involution the mammary gland is exposed to milk stasis, programmed cell death and stromal reorganization to clear the differentiated milk-producing cells. Not surprisingly, the signaling pathways responsible for bringing about these changes in breast cells are often subverted during the process of tumorigenesis. The STAT family of proteins is involved in every stage of mammary gland development, and is also frequently implicated in breast tumorigenesis. While the roles of STAT3 and STAT5 during mammary gland development and tumorigenesis are well studied, others members, e.g. STAT1 and STAT6, have only recently been observed to play a role in mammary gland biology. Continued investigation into the STAT protein network in the mammary gland will likely yield new biomarkers and risk factors for breast cancer, and may also lead to novel prophylactic or therapeutic strategies against breast cancer.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: S
authors.initials: S
authors.lastname: Haricharan
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA. Electronic address: liyi@bcm.edu.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D002470:Cell Survival; D005260:Female; D006801:Humans; D008321:Mammary Glands, Animal / Q000378:metabolism / Q000473:pathology*; D042361:Mammary Glands, Human / Q000378:metabolism / Q000473:pathology*; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D050791:STAT Transcription Factors
keywords: Breast cancer; Involution; Lactation; Mammary gland development; Pregnancy; STATs
references.citation: Oncogene. 2010 Feb 11;29(6):920-9
references.pmid: 19915608
references.citation: Cancer Res. 2012 Jun 1;72(11):2768-79
references.pmid: 22472119
references.citation: Development. 2003 Nov;130(21):5257-68
references.pmid: 12954715
references.citation: Mol Endocrinol. 1996 Dec;10(12):1496-506
references.pmid: 8961260
references.citation: Mol Endocrinol. 2006 Mar;20(3):675-85
references.pmid: 16293640
references.citation: Development. 2007 Aug;134(15):2739-50
references.pmid: 17611223
references.citation: Mol Cell Biol. 2004 Sep;24(18):8037-47
references.pmid: 15340066
references.citation: Dev Biol. 2009 May 15;329(2):227-41
references.pmid: 19269284
references.citation: Genome Res. 2013 Mar;23(3):462-72
references.pmid: 23212947
references.citation: Ann Surg Oncol. 2006 Jan;13(1):118-24
references.pmid: 16372153
references.citation: Dev Biol. 2001 Jan 1;229(1):163-75
references.pmid: 11133161
references.citation: FEBS Lett. 2004 Aug 13;572(1-3):238-44
references.pmid: 15304355
references.citation: Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7556-61
references.pmid: 9636188
references.citation: Endocrinology. 2010 Dec;151(12):5730-40
references.pmid: 20881248
references.citation: J Dairy Sci. 2006 Nov;89(11):4433-7
references.pmid: 17033032
references.citation: Dev Biol. 2010 Oct 15;346(2):196-203
references.pmid: 20691178
references.citation: Nature. 1996 Jul 11;382(6587):171-4
references.pmid: 8700208
references.citation: Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3425-30
references.pmid: 9096410
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14533-8
references.pmid: 18779591
references.citation: Front Biosci (Landmark Ed). 2012 Jan 01;17:1232-50
references.pmid: 22201800
references.citation: Nature. 1996 Apr 18;380(6575):630-3
references.pmid: 8602264
references.citation: Immunity. 1996 Mar;4(3):313-9
references.pmid: 8624821
references.citation: Cell. 1996 Feb 9;84(3):443-50
references.pmid: 8608598
references.citation: Cancer Cell. 2009 Aug 4;16(2):91-102
references.pmid: 19647220
references.citation: Nat Cell Biol. 2005 Apr;7(4):392-8
references.pmid: 15793565
references.citation: Science. 1997 Sep 12;277(5332):1630-5
references.pmid: 9287210
references.citation: Genes Dev. 1997 Jan 15;11(2):179-86
references.pmid: 9009201
references.citation: Histopathology. 2012 Jun;60(7):1125-32
references.pmid: 22320867
references.citation: Dev Biol. 2007 Mar 1;303(1):29-44
references.pmid: 17222404
references.citation: Mol Endocrinol. 2007 Aug;21(8):1877-92
references.pmid: 17519353
references.citation: Bull World Health Organ. 1970;43(2):209-21
references.pmid: 5312521
references.citation: Stem Cells. 1999;17(3):138-46
references.pmid: 10342556
references.citation: J Clin Oncol. 2011 Jun 20;29(18):2448-58
references.pmid: 21576635
references.citation: Science. 1995 Mar 3;267(5202):1347-9
references.pmid: 7871432
references.citation: J Mammary Gland Biol Neoplasia. 2001 Jan;6(1):115-27
references.pmid: 11467447
references.citation: Genes Dev. 2003 Aug 15;17(16):1992-2005
references.pmid: 12923054
references.citation: Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9623-8
references.pmid: 22623533
references.citation: FEBS Lett. 1996 Oct 28;396(1):77-80
references.pmid: 8906870
references.citation: Breast Cancer Res. 2012 Jan 20;14(1):R16
references.pmid: 22264274
references.citation: Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18490-5
references.pmid: 19001271
references.citation: J Biol Chem. 2004 Oct 15;279(42):44093-100
references.pmid: 15292206
references.citation: Nucleic Acids Res. 2013 Feb 1;41(3):1622-36
references.pmid: 23275557
references.citation: Int J Cancer. 2009 May 1;124(9):2124-34
references.pmid: 19142869
references.citation: Cell. 1999 Jul 23;98(2):181-91
references.pmid: 10428030
references.citation: Oncogene. 2010 Sep 30;29(39):5359-69
references.pmid: 20639901
references.citation: J Biol Chem. 2004 Apr 9;279(15):15114-23
references.pmid: 14701810
references.citation: Br J Cancer. 1995 Apr;71(4):840-4
references.pmid: 7710952
references.citation: Int J Cancer. 2004 Feb 20;108(5):665-71
references.pmid: 14696092
references.citation: Mol Endocrinol. 2008 Dec;22(12):2677-88
references.pmid: 18927239
references.citation: PLoS One. 2009 Nov 23;4(11):e7965
references.pmid: 19956757
references.citation: Endocr Relat Cancer. 2006 Sep;13(3):885-93
references.pmid: 16954437
references.citation: Stem Cells. 2013 Feb;31(2):248-58
references.pmid: 23169551
references.citation: Mol Endocrinol. 2001 Nov;15(11):1929-40
references.pmid: 11682624
references.citation: J Biol Chem. 2003 Sep 5;278(36):34133-40
references.pmid: 12832402
references.citation: Breast Cancer Res. 2004;6(2):R92-109
references.pmid: 14979921
references.citation: Nature. 2005 Apr 14;434(7035):864-70
references.pmid: 15829956
references.citation: Cell. 1998 May 29;93(5):827-39
references.pmid: 9630226
references.citation: Cell. 1999 Aug 6;98(3):295-303
references.pmid: 10458605
references.citation: Breast. 2013 Jun;22(3):344-50
references.pmid: 22981738
references.citation: J Immunol. 1998 Nov 1;161(9):4652-60
references.pmid: 9794394
references.citation: PLoS One. 2012;7(10):e46624
references.pmid: 23056374
references.citation: Breast Cancer Res. 2000;2(2):86-90
references.pmid: 11250696
references.citation: Oncogene. 2005 Jan 20;24(4):552-60
references.pmid: 15580303
references.citation: Clin Cancer Res. 2002 Oct;8(10):3065-74
references.pmid: 12374673
references.citation: Development. 2013 Jan 1;140(1):117-25
references.pmid: 23154416
references.citation: J Clin Oncol. 2004 Jun 1;22(11):2053-60
references.pmid: 15169792
references.citation: EMBO J. 2010 Mar 3;29(5):956-68
references.pmid: 20075866
references.citation: J Pathol. 2012 May;227(1):106-17
references.pmid: 22081431
references.citation: J Biol Chem. 1996 Mar 8;271(10):5790-4
references.pmid: 8621447
references.citation: Genes Dev. 2012 May 15;26(10):1086-97
references.pmid: 22588720
references.citation: Exp Cell Res. 2003 Jan 1;282(1):35-47
references.pmid: 12490192
references.citation: Mol Cell Biol. 2004 May;24(9):4038-48
references.pmid: 15082796
references.citation: Endocrinology. 2010 Jun;151(6):2876-85
references.pmid: 20392833
references.citation: Nat Cell Biol. 2011 Mar;13(3):303-9
references.pmid: 21336304
references.citation: Nature. 1996 Apr 18;380(6575):627-30
references.pmid: 8602263
references.citation: Cell Death Differ. 2012 Mar;19(3):511-22
references.pmid: 21941370
references.citation: Cancer Biol Ther. 2006 Mar;5(3):292-7
references.pmid: 16418573
references.citation: Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3728-33
references.pmid: 20133707
references.citation: Endocrinology. 2011 May;152(5):1935-47
references.pmid: 21427222
references.citation: Cell. 1996 Feb 9;84(3):431-42
references.pmid: 8608597
references.citation: Science. 1994 Jun 3;264(5164):1415-21
references.pmid: 8197455
references.citation: Blood. 2009 Dec 3;114(24):5034-43
references.pmid: 19808698
references.citation: Cancer Res. 2010 Feb 15;70(4):1711-21
references.pmid: 20124477
references.citation: Genes Dev. 1999 Oct 1;13(19):2604-16
references.pmid: 10521404
references.citation: Mol Endocrinol. 2011 Apr;25(4):597-610
references.pmid: 21310852
references.citation: Int J Oncol. 2010 May;36(5):1243-51
references.pmid: 20372799
references.citation: Cancer Res. 2011 May 15;71(10):3720-31
references.pmid: 21464042
references.citation: Int J Cancer. 2006 Sep 15;119(6):1468-74
references.pmid: 16642468
references.citation: J Biol Chem. 2006 Nov 10;281(45):34374-80
references.pmid: 16959766
references.citation: Development. 2005 Mar;132(5):1147-60
references.pmid: 15689376
references.citation: Oncogene. 2004 Sep 9;23(41):6980-5
references.pmid: 15286714
references.citation: Development. 2003 Aug;130(15):3459-68
references.pmid: 12810593
references.citation: Stem Cells. 2010 May;28(5):928-38
references.pmid: 20235097
references.citation: Clin Cancer Res. 2006 Jan 1;12(1):20-8
references.pmid: 16397019
references.citation: Genes Dev. 2012 Oct 1;26(19):2154-68
references.pmid: 23028142
references.citation: Neoplasia. 2010 Nov;12(11):899-905
references.pmid: 21076615
references.citation: Genes Dev. 1995 Apr 15;9(8):984-94
references.pmid: 7774815
references.citation: J Immunol. 2002 Nov 15;169(10):5796-804
references.pmid: 12421960
references.citation: Genes Dev. 2009 Oct 15;23(20):2382-7
references.pmid: 19833766
references.citation: J Immunol. 2000 Dec 1;165(11):6015-9
references.pmid: 11086031
references.citation: Mol Cell Biol. 2004 Jun;24(12):5510-20
references.pmid: 15169911
references.citation: Mol Cell. 2010 Aug 27;39(4):493-506
references.pmid: 20797623
references.citation: Mol Endocrinol. 2006 May;20(5):1177-87
references.pmid: 16469767
references.citation: J Immunol. 2003 Feb 15;170(4):2014-21
references.pmid: 12574371
references.citation: Development. 2002 Mar;129(6):1377-86
references.pmid: 11880347
references.citation: Methods Enzymol. 2010;484:329-55
references.pmid: 21036240
references.citation: Cancer. 2012 Jul 1;118(13):3226-8
references.pmid: 22086839
references.citation: Blood. 2009 Apr 23;113(17):4052-62
references.pmid: 19144991
references.citation: Breast Cancer Res. 2011 Apr 26;13(2):R47
references.pmid: 21521526
references.citation: Cell Cycle. 2011 Mar 1;10(5):794-804
references.pmid: 21311224
references.citation: Development. 2012 Sep;139(17):3147-56
references.pmid: 22833129
references.citation: Endocrinology. 2002 Sep;143(9):3641-50
references.pmid: 12193580
references.citation: Cancer Res. 2010 Mar 15;70(6):2558-67
references.pmid: 20215508
references.citation: Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6221-4
references.pmid: 8692794
references.citation: Int J Cancer. 2004 Nov 20;112(4):607-19
references.pmid: 15382041
references.citation: Genes Dev. 2001 Jul 1;15(13):1631-6
references.pmid: 11445538
references.citation: Mol Cell Biol. 2010 Jun;30(12):2957-70
references.pmid: 20385773
references.citation: J Clin Endocrinol Metab. 2010 Jan;95(1):271-9
references.pmid: 19897676
references.citation: Genes Dev. 1999 Jun 1;13(11):1361-6
references.pmid: 10364154
references.citation: Immunity. 2000 Dec;13(6):795-804
references.pmid: 11163195
references.citation: EMBO J. 2003 Feb 17;22(4):893-904
references.pmid: 12574125
references.citation: Cell. 1998 May 29;93(5):841-50
references.pmid: 9630227
references.citation: Clin Cancer Res. 2012 Jun 1;18(11):3015-21
references.pmid: 22615451
references.citation: J Cell Physiol. 1996 Sep;168(3):559-69
references.pmid: 8816910
references.citation: Science. 1996 Sep 20;273(5282):1717-9
references.pmid: 8781235
references.citation: Mol Endocrinol. 2002 Mar;16(3):563-70
references.pmid: 11875116