title: Key signalling nodes in mammary gland development and cancer. Signalling downstream of PI3 kinase in mammary epithelium: a play in 3 Akts.
abstract: The protein serine/threonine kinase Akt, also known as protein kinase B (PKB), is arguably the most important signalling nexus in the cell. Akt integrates a plethora of extracellular signals to generate diverse outcomes, including proliferation, motility, growth, glucose homeostasis, survival, and cell death. The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is the second most frequently mutated pathway in cancer, after p53, and mutations in components of this pathway are found in around 70% of breast cancers. Thus, understanding how Akt relays input signals to downstream effectors is critically important for the design of therapeutic strategies to combat breast cancer. In this review, we will discuss the various signals upstream of Akt that impact on its activity, how Akt integrates these signals and modulates the activity of downstream targets to control mammary gland development, and how mutations in components of the pathway result in breast cancer.
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, UK. jaw64@cam.ac.uk
authors.forename: Julie A
authors.initials: JA
authors.lastname: Wickenden
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Watson
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D042361:Mammary Glands, Human / Q000378:metabolism*; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D019869:Phosphatidylinositol 3-Kinases; C494918:AKT1 protein, human; C494921:AKT2 protein, human; C491754:AKT3 protein, human; D051057:Proto-Oncogene Proteins c-akt
references.citation: Cancer Res. 2008 Apr 1;68(7):2122-31
references.pmid: 18381417
references.citation: Mol Endocrinol. 2001 Jun;15(6):867-81
references.pmid: 11376107
references.citation: Cell. 2004 Apr 16;117(2):225-37
references.pmid: 15084260
references.citation: Breast Cancer Res. 2008;10(4):R70
references.pmid: 18700973
references.citation: Nat Cell Biol. 2008 Feb;10(2):127-37
references.pmid: 18204440
references.citation: Science. 2002 May 31;296(5573):1655-7
references.pmid: 12040186
references.citation: Oncogene. 2002 Jan 10;21(2):198-206
references.pmid: 11803463
references.citation: Cell Res. 2008 Aug;18(8):807-16
references.pmid: 18626510
references.citation: Endocrinology. 2002 May;143(5):1872-9
references.pmid: 11956170
references.citation: Mol Cell. 2005 Nov 23;20(4):539-50
references.pmid: 16307918
references.citation: Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):429-34
references.pmid: 9892650
references.citation: Cell Cycle. 2009 Sep 1;8(17):2728-32
references.pmid: 19652529
references.citation: J Biol Chem. 2009 Jul 10;284(28):19018-26
references.pmid: 19435886
references.citation: Clin Cancer Res. 2004 Dec 1;10(23):8059-67
references.pmid: 15585641
references.citation: Cell Cycle. 2005 Jul;4(7):897-900
references.pmid: 15970662
references.citation: Nat Cell Biol. 2005 Apr;7(4):392-8
references.pmid: 15793565
references.citation: Gene. 2006 Jun 7;374:1-9
references.pmid: 16675164
references.citation: J Clin Invest. 2002 Sep;110(6):815-25
references.pmid: 12235113
references.citation: J Mammary Gland Biol Neoplasia. 2000 Jan;5(1):31-42
references.pmid: 10791766
references.citation: Mol Cell Biol. 2001 Mar;21(6):2203-12
references.pmid: 11238953
references.citation: Cancer Res. 2008 Dec 1;68(23):9643-53
references.pmid: 19047141
references.citation: Trends Biochem Sci. 2005 Apr;30(4):194-204
references.pmid: 15817396
references.citation: Nature. 2009 Oct 22;461(7267):1084-91
references.pmid: 19847259
references.citation: Cancer Res. 2009 Jun 15;69(12):5057-64
references.pmid: 19491266
references.citation: J Lipid Res. 2003 Jun;44(6):1100-12
references.pmid: 12700340
references.citation: Development. 2002 Sep;129(17):4159-70
references.pmid: 12163417
references.citation: Science. 1997 May 30;276(5317):1418-20
references.pmid: 9162009
references.citation: Nature. 1999 Sep 2;401(6748):86-90
references.pmid: 10485711
references.citation: Gene Ther. 2003 Nov;10(23):1961-9
references.pmid: 14528320
references.citation: Genes Dev. 2003 Jun 1;17(11):1352-65
references.pmid: 12782654
references.citation: Cancer Res. 2004 May 1;64(9):3171-8
references.pmid: 15126356
references.citation: Mol Biol Cell. 2001 May;12(5):1445-55
references.pmid: 11359934
references.citation: Cancer Res. 2009 Aug 1;69(15):6299-306
references.pmid: 19602588
references.citation: Breast Cancer Res Treat. 2008 Nov;112(2):217-27
references.pmid: 18074223
references.citation: Cancer Res. 2002 Jun 15;62(12):3538-43
references.pmid: 12068001
references.citation: Endocrinology. 2009 Aug;150(8):3611-9
references.pmid: 19406949
references.citation: BMC Mol Biol. 2001;2:2
references.pmid: 11178110
references.citation: Cancer Res. 2009 May 15;69(10):4545-52
references.pmid: 19417140
references.citation: J Cell Biol. 2005 Dec 19;171(6):1023-34
references.pmid: 16365168
references.citation: Biol Cell. 2009 Jan;101(1):13-29
references.pmid: 19055486
references.citation: Nature. 2007 Jul 26;448(7152):439-44
references.pmid: 17611497
references.citation: Genes Dev. 2008 Jun 1;22(11):1490-500
references.pmid: 18519641
references.citation: Sci Signal. 2009 Oct 13;2(92):ra62
references.pmid: 19825827
references.citation: Cell. 1995 Aug 25;82(4):621-30
references.pmid: 7664341
references.citation: Nat Rev Genet. 2006 Aug;7(8):606-19
references.pmid: 16847462
references.citation: J Cell Physiol. 2008 Nov;217(2):468-77
references.pmid: 18561256
references.citation: Cell Metab. 2006 Dec;4(6):475-90
references.pmid: 17141631