title: Prolactin and estrogen enhance the activity of activating protein 1 in breast cancer cells: role of extracellularly regulated kinase 1/2-mediated signals to c-fos.
abstract: Despite the important roles of both prolactin (PRL) and 17beta-estradiol (E2) in normal mammary development as well as in breast cancer, and coexpression of the estrogen receptor (ER) and PRL receptor in many mammary tumors, the interactions between PRL and E2 in breast cancer have not been well studied. The activating protein 1 (AP-1) transcription factor, a known regulator of processes essential for normal growth and development as well as carcinogenesis, is a potential site for cross-talk between these hormones in breast cancer cells. Here we demonstrate that PRL and E2 cooperatively enhance the activity of AP-1 in MCF-7-derived cells. In addition to the acute PRL-induced ERK1/2 activation, PRL and E2 also individually elicited delayed, sustained rises in levels of phosphorylated p38 and especially ERK1/2. Together, these hormones increased the dynamic phosphorylation of ERK1/2 and c-Fos, and induced c-fos promoter activity. Synergistic activation of the transcription factor, Elk-1, reflected the PRL-E2 interaction at ERK1/2 and is a likely mechanism for activation of the c-fos promoter via the serum response element. The enhanced AP-1 activity resulting from the interaction of these hormones may increase expression of many target genes that are critical for oncogenesis and may contribute to neoplastic progression.
authors.affiliation: Department of Comparative Biosciences, University of Wisconsin, 2015 Linden Drive, Madison, WI 53706, USA.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Gutzman
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Nikolai
authors.forename: Debra E
authors.initials: DE
authors.lastname: Rugowski
authors.forename: Jyoti J
authors.initials: JJ
authors.lastname: Watters
authors.forename: Linda A
authors.initials: LA
authors.lastname: Schuler
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation; D011388:Prolactin / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D004967:Estrogens; D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1; D011388:Prolactin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
references.citation: Science. 1997 Aug 1;277(5326):693-6
references.pmid: 9235893
references.citation: Mol Endocrinol. 2002 Jan;16(1):45-57
references.pmid: 11773438
references.citation: Mol Endocrinol. 2004 Dec;18(12):3064-75
references.pmid: 15319452
references.citation: Mol Endocrinol. 2000 Sep;14(9):1434-47
references.pmid: 10976921
references.citation: Endocr Rev. 2003 Feb;24(1):1-27
references.pmid: 12588805
references.citation: Breast Cancer Res Treat. 2003 Feb;77(3):265-75
references.pmid: 12602926
references.citation: Mol Endocrinol. 1999 Oct;13(10):1672-85
references.pmid: 10517669
references.citation: Nucleic Acids Res. 1990 Sep 11;18(17):5097-106
references.pmid: 2119495
references.citation: Br J Cancer. 2002 Oct 7;87(8):876-82
references.pmid: 12373602
references.citation: J Biol Chem. 1995 Jul 14;270(28):16483-6
references.pmid: 7622446
references.citation: J Biol Chem. 2000 Jan 7;275(1):479-86
references.pmid: 10617642
references.citation: Mol Cell Biol. 2002 Aug;22(16):5835-45
references.pmid: 12138194
references.citation: Mol Cell Biol. 2004 Aug;24(16):7260-74
references.pmid: 15282324
references.citation: J Steroid Biochem Mol Biol. 2002 Feb;80(2):137-48
references.pmid: 11897499
references.citation: Cell Growth Differ. 2000 Feb;11(2):99-110
references.pmid: 10714766
references.citation: Oncogene. 1996 Sep 19;13(6):1139-45
references.pmid: 8808687
references.citation: Clin Cancer Res. 2004 Jan 1;10(1 Pt 2):331S-6S
references.pmid: 14734488
references.citation: Mol Endocrinol. 2004 Mar;18(3):521-32
references.pmid: 14684847
references.citation: Cancer Cell. 2004 Mar;5(3):207-13
references.pmid: 15050912
references.citation: Dev Dyn. 2001 Oct;222(2):192-205
references.pmid: 11668597
references.citation: J Natl Cancer Inst. 1999 Apr 7;91(7):629-34
references.pmid: 10203283
references.citation: J Biol Chem. 1996 Apr 26;271(17):9942-6
references.pmid: 8626631
references.citation: Nat Cell Biol. 2002 May;4(5):E131-6
references.pmid: 11988758
references.citation: Mol Endocrinol. 2003 Mar;17(3):309-17
references.pmid: 12554774
references.citation: J Biol Chem. 1999 Dec 10;274(50):35461-8
references.pmid: 10585417
references.citation: Oncogene. 2001 Apr 30;20(19):2438-52
references.pmid: 11402339
references.citation: Nat Rev Cancer. 2003 Nov;3(11):859-68
references.pmid: 14668816
references.citation: Nucl Recept. 2004 Jun 14;2(1):3
references.pmid: 15196329
references.citation: Gene. 2004 Jan 7;324:1-14
references.pmid: 14693367
references.citation: J Biol Chem. 2002 Jun 21;277(25):22558-65
references.pmid: 11960991
references.citation: Immunity. 1998 Jan;8(1):89-95
references.pmid: 9462514
references.citation: Oncogene. 1994 Mar;9(3):791-9
references.pmid: 8108121
references.citation: Mol Cell Biol. 2004 Jun;24(11):4835-47
references.pmid: 15143177
references.citation: J Biol Chem. 2001 Sep 28;276(39):36361-9
references.pmid: 11477071
references.citation: Cancer Res. 1977 Mar;37(3):792-9
references.pmid: 189915
references.citation: Mol Endocrinol. 2002 Apr;16(4):774-84
references.pmid: 11923474
references.citation: Mol Endocrinol. 2002 Oct;16(10):2188-201
references.pmid: 12351685
references.citation: J Steroid Biochem Mol Biol. 1990 Dec 20;37(6):977-81
references.pmid: 2285609
references.citation: Biochem J. 2000 Oct 1;351(Pt 1):95-105
references.pmid: 10998351
references.citation: Endocrinology. 1997 Sep;138(9):4030-3
references.pmid: 9275096
references.citation: J Steroid Biochem Mol Biol. 2004 Jan;88(1):69-77
references.pmid: 15026085
references.citation: J Steroid Biochem Mol Biol. 1992 Mar;41(3-8):315-21
references.pmid: 1562509
references.citation: J Steroid Biochem Mol Biol. 1996 Nov;59(3-4):261-9
references.pmid: 9010318
references.citation: J Biol Chem. 1995 Jun 16;270(24):14500-4
references.pmid: 7782312
references.citation: J Biol Chem. 2001 Mar 23;276(12):8836-40
references.pmid: 11121427
references.citation: J Steroid Biochem Mol Biol. 2003 Oct;87(1):1-25
references.pmid: 14630087
references.citation: Mol Endocrinol. 2003 Oct;17(10):2013-27
references.pmid: 12855746
references.citation: Mol Carcinog. 1996 Mar;15(3):215-26
references.pmid: 8597534
references.citation: Endocr Rev. 1999 Jun;20(3):358-417
references.pmid: 10368776
references.citation: Semin Cancer Biol. 2001 Oct;11(5):339-52
references.pmid: 11562176
references.citation: Mol Cell Biol. 2004 Jun;24(12):5510-20
references.pmid: 15169911
references.citation: J Biol Chem. 2001 Jun 22;276(25):22177-82
references.pmid: 11301320
references.citation: Dev Cell. 2001 Oct;1(4):467-75
references.pmid: 11703938
references.citation: Cancer Res. 1984 May;44(5):1963-8
references.pmid: 6324992
references.citation: J Mammary Gland Biol Neoplasia. 1999 Jan;4(1):79-88
references.pmid: 10219908
references.citation: Mol Endocrinol. 1988 Jun;2(6):543-55
references.pmid: 3047554
references.citation: Clin Cancer Res. 1999 Feb;5(2):251-6
references.pmid: 10037172
references.citation: J Biol Chem. 2001 Apr 27;276(17):13615-21
references.pmid: 11278408
references.citation: Mol Endocrinol. 2000 Oct;14(10):1592-602
references.pmid: 11043575
references.citation: Nat Cell Biol. 2002 Aug;4(8):556-64
references.pmid: 12134156
references.citation: Oncogene. 1993 Aug;8(8):2183-91
references.pmid: 7687761
references.citation: Mol Endocrinol. 2000 Apr;14(4):564-75
references.pmid: 10770493
references.citation: J Biol Chem. 1992 Jan 25;267(3):1823-8
references.pmid: 1730720
references.citation: Mol Cell Biol. 1995 Oct;15(10):5682-7
references.pmid: 7565719
references.citation: Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7829-34
references.pmid: 10869427
references.citation: J Biol Chem. 1993 Jul 5;268(19):14103-8
references.pmid: 8314777
references.citation: Int J Cancer. 1999 Oct 22;84(5):533-8
references.pmid: 10502734
references.citation: Mol Endocrinol. 2002 Dec;16(12):2675-91
references.pmid: 12456789
references.citation: Curr Opin Genet Dev. 1994 Feb;4(1):96-101
references.pmid: 8193547
references.citation: Bioessays. 2000 Sep;22(9):818-26
references.pmid: 10944584
references.citation: Int J Cancer. 2000 Mar 20;89(2):177-86
references.pmid: 10754497
references.citation: J Biol Chem. 1992 Feb 25;267(6):3771-7
references.pmid: 1371278
references.citation: Endocrinology. 2003 Dec;144(12):5300-7
references.pmid: 12970160
references.citation: Crit Rev Oncog. 1993;4(4):361-88
references.pmid: 8353138
references.citation: Mol Endocrinol. 2004 Feb;18(2):412-21
references.pmid: 14605098
references.citation: Endocr Rev. 2001 Apr;22(2):153-83
references.pmid: 11294822
references.citation: Oncogene. 2001 Apr 30;20(19):2453-64
references.pmid: 11402340
references.citation: Curr Opin Cell Biol. 2000 Apr;12(2):186-92
references.pmid: 10712927
references.citation: Endocrinology. 1998 Apr;139(4):1981-90
references.pmid: 9528985
references.citation: Endocrinology. 2002 Mar;143(3):930-40
references.pmid: 11861515
references.citation: J Biol Chem. 1994 May 6;269(18):13337-45
references.pmid: 8175764
references.citation: J Clin Endocrinol Metab. 1997 Nov;82(11):3692-9
references.pmid: 9360527
references.citation: J Steroid Biochem Mol Biol. 2000 Nov 30;74(5):311-7
references.pmid: 11162939
references.citation: EMBO J. 1995 Oct 16;14(20):5037-47
references.pmid: 7588632
references.citation: Int J Cancer. 2000 Aug 15;87(4):468-72
references.pmid: 10918184
references.citation: Mol Endocrinol. 2004 Nov;18(11):2700-13
references.pmid: 15297603
references.citation: J Biol Chem. 2001 Apr 13;276(15):11590-8
references.pmid: 11145955