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.
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.
Gutzman
Jennifer H
JH
Department of Comparative Biosciences, University of Wisconsin, 2015 Linden Drive, Madison, WI 53706, USA.
Nikolai
Sarah E
SE
Rugowski
Debra E
DE
Watters
Jyoti J
JJ
Schuler
Linda A
LA
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*
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
Science. 1997 Aug 1;277(5326):693-6
9235893
Mol Endocrinol. 2002 Jan;16(1):45-57
11773438
Mol Endocrinol. 2004 Dec;18(12):3064-75
15319452
Mol Endocrinol. 2000 Sep;14(9):1434-47
10976921
Endocr Rev. 2003 Feb;24(1):1-27
12588805
Breast Cancer Res Treat. 2003 Feb;77(3):265-75
12602926
Mol Endocrinol. 1999 Oct;13(10):1672-85
10517669
Nucleic Acids Res. 1990 Sep 11;18(17):5097-106
2119495
Br J Cancer. 2002 Oct 7;87(8):876-82
12373602
J Biol Chem. 1995 Jul 14;270(28):16483-6
7622446
J Biol Chem. 2000 Jan 7;275(1):479-86
10617642
Mol Cell Biol. 2002 Aug;22(16):5835-45
12138194
Mol Cell Biol. 2004 Aug;24(16):7260-74
15282324
J Steroid Biochem Mol Biol. 2002 Feb;80(2):137-48
11897499
Cell Growth Differ. 2000 Feb;11(2):99-110
10714766
Oncogene. 1996 Sep 19;13(6):1139-45
8808687
Clin Cancer Res. 2004 Jan 1;10(1 Pt 2):331S-6S
14734488
Mol Endocrinol. 2004 Mar;18(3):521-32
14684847
Cancer Cell. 2004 Mar;5(3):207-13
15050912
Dev Dyn. 2001 Oct;222(2):192-205
11668597
J Natl Cancer Inst. 1999 Apr 7;91(7):629-34
10203283
J Biol Chem. 1996 Apr 26;271(17):9942-6
8626631
Nat Cell Biol. 2002 May;4(5):E131-6
11988758
Mol Endocrinol. 2003 Mar;17(3):309-17
12554774
J Biol Chem. 1999 Dec 10;274(50):35461-8
10585417
Oncogene. 2001 Apr 30;20(19):2438-52
11402339
Nat Rev Cancer. 2003 Nov;3(11):859-68
14668816
Nucl Recept. 2004 Jun 14;2(1):3
15196329
Gene. 2004 Jan 7;324:1-14
14693367
J Biol Chem. 2002 Jun 21;277(25):22558-65
11960991
Immunity. 1998 Jan;8(1):89-95
9462514
Oncogene. 1994 Mar;9(3):791-9
8108121
Mol Cell Biol. 2004 Jun;24(11):4835-47
15143177
J Biol Chem. 2001 Sep 28;276(39):36361-9
11477071
Cancer Res. 1977 Mar;37(3):792-9
189915
Mol Endocrinol. 2002 Apr;16(4):774-84
11923474
Mol Endocrinol. 2002 Oct;16(10):2188-201
12351685
J Steroid Biochem Mol Biol. 1990 Dec 20;37(6):977-81
2285609
Biochem J. 2000 Oct 1;351(Pt 1):95-105
10998351
Endocrinology. 1997 Sep;138(9):4030-3
9275096
J Steroid Biochem Mol Biol. 2004 Jan;88(1):69-77
15026085
J Steroid Biochem Mol Biol. 1992 Mar;41(3-8):315-21
1562509
J Steroid Biochem Mol Biol. 1996 Nov;59(3-4):261-9
9010318
J Biol Chem. 1995 Jun 16;270(24):14500-4
7782312
J Biol Chem. 2001 Mar 23;276(12):8836-40
11121427
J Steroid Biochem Mol Biol. 2003 Oct;87(1):1-25
14630087
Mol Endocrinol. 2003 Oct;17(10):2013-27
12855746
Mol Carcinog. 1996 Mar;15(3):215-26
8597534
Endocr Rev. 1999 Jun;20(3):358-417
10368776
Semin Cancer Biol. 2001 Oct;11(5):339-52
11562176
Mol Cell Biol. 2004 Jun;24(12):5510-20
15169911
J Biol Chem. 2001 Jun 22;276(25):22177-82
11301320
Dev Cell. 2001 Oct;1(4):467-75
11703938
Cancer Res. 1984 May;44(5):1963-8
6324992
J Mammary Gland Biol Neoplasia. 1999 Jan;4(1):79-88
10219908
Mol Endocrinol. 1988 Jun;2(6):543-55
3047554
Clin Cancer Res. 1999 Feb;5(2):251-6
10037172
J Biol Chem. 2001 Apr 27;276(17):13615-21
11278408
Mol Endocrinol. 2000 Oct;14(10):1592-602
11043575
Nat Cell Biol. 2002 Aug;4(8):556-64
12134156
Oncogene. 1993 Aug;8(8):2183-91
7687761
Mol Endocrinol. 2000 Apr;14(4):564-75
10770493
J Biol Chem. 1992 Jan 25;267(3):1823-8
1730720
Mol Cell Biol. 1995 Oct;15(10):5682-7
7565719
Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7829-34
10869427
J Biol Chem. 1993 Jul 5;268(19):14103-8
8314777
Int J Cancer. 1999 Oct 22;84(5):533-8
10502734
Mol Endocrinol. 2002 Dec;16(12):2675-91
12456789
Curr Opin Genet Dev. 1994 Feb;4(1):96-101
8193547
Bioessays. 2000 Sep;22(9):818-26
10944584
Int J Cancer. 2000 Mar 20;89(2):177-86
10754497
J Biol Chem. 1992 Feb 25;267(6):3771-7
1371278
Endocrinology. 2003 Dec;144(12):5300-7
12970160
Crit Rev Oncog. 1993;4(4):361-88
8353138
Mol Endocrinol. 2004 Feb;18(2):412-21
14605098
Endocr Rev. 2001 Apr;22(2):153-83
11294822
Oncogene. 2001 Apr 30;20(19):2453-64
11402340
Curr Opin Cell Biol. 2000 Apr;12(2):186-92
10712927
Endocrinology. 1998 Apr;139(4):1981-90
9528985
Endocrinology. 2002 Mar;143(3):930-40
11861515
J Biol Chem. 1994 May 6;269(18):13337-45
8175764
J Clin Endocrinol Metab. 1997 Nov;82(11):3692-9
9360527
J Steroid Biochem Mol Biol. 2000 Nov 30;74(5):311-7
11162939
EMBO J. 1995 Oct 16;14(20):5037-47
7588632
Int J Cancer. 2000 Aug 15;87(4):468-72
10918184
Mol Endocrinol. 2004 Nov;18(11):2700-13
15297603
J Biol Chem. 2001 Apr 13;276(15):11590-8
11145955