Notch-1 Activates Estrogen Receptor-alpha-dependent Transcription Via IKKalpha in Breast Cancer Cells

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2009 Oct 20

PMID 19838210

Citations 81

Authors

L Hao

P Rizzo

C Osipo

A Pannuti

D Wyatt

L W-K Cheung

G Sonenshein

B A Osborne

L Miele

Affiliations

Soon will be listed here.

Abstract

Approximately 80% of breast cancers express the estrogen receptor-alpha (ERalpha) and are treated with anti-estrogens. Resistance to these agents is a major cause of mortality. We have shown that estrogen inhibits Notch, whereas anti-estrogens or estrogen withdrawal activate Notch signaling. Combined inhibition of Notch and estrogen signaling has synergistic effects in ERalpha-positive breast cancer models. However, the mechanisms whereby Notch-1 promotes the growth of ERalpha-positive breast cancer cells are unknown. Here, we demonstrate that Notch-1 increases the transcription of ERalpha-responsive genes in the presence or absence of estrogen via a novel chromatin crosstalk mechanism. Our data support a model in which Notch-1 can activate the transcription of ERalpha-target genes via IKKalpha-dependent cooperative chromatin recruitment of Notch-CSL-MAML1 transcriptional complexes (NTC) and ERalpha, which promotes the recruitment of p300. CSL binding elements frequently occur in close proximity to estrogen-responsive elements (EREs) in the human and mouse genomes. Our observations suggest that a hitherto unknown Notch-1/ERalpha chromatin crosstalk mediates Notch signaling effects in ERalpha-positive breast cancer cells and contributes to regulate the transcriptional functions of ERalpha itself.

Citing Articles

Mechanisms of endocrine resistance in hormone receptor-positive breast cancer.

Gao Y, Yu Y, Zhang M, Yu W, Kang L Front Oncol. 2024; 14:1448687.

PMID: 39544302 PMC: 11560879. DOI: 10.3389/fonc.2024.1448687.

17β-estradiol inhibits Notch1 activation in murine macrophage cell line RAW 264.7.

Severi P, Ascierto A, Marracino L, Ouambo Talla A, Aquila G, Martino V Mol Biol Rep. 2024; 51(1):1134.

PMID: 39514048 DOI: 10.1007/s11033-024-10058-x.

Design and Synthesis of Novel Aminoindazole-pyrrolo[2,3-]pyridine Inhibitors of IKKα That Selectively Perturb Cellular Non-Canonical NF-κB Signalling.

Riley C, Ammar U, Alsfouk A, Anthony N, Baiget J, Berretta G Molecules. 2024; 29(15).

PMID: 39124921 PMC: 11314561. DOI: 10.3390/molecules29153515.

The Efficacy of CB-103, a First-in-Class Transcriptional Notch Inhibitor, in Preclinical Models of Breast Cancer.

Vigolo M, Urech C, Lamy S, Monticone G, Zabaleta J, Hossain F Cancers (Basel). 2023; 15(15).

PMID: 37568775 PMC: 10416998. DOI: 10.3390/cancers15153957.

IKKα promotes lung adenocarcinoma growth through ERK signaling activation via DARPP-32-mediated inhibition of PP1 activity.

Alam S, Wang L, Zhu Z, Hoeppner L NPJ Precis Oncol. 2023; 7(1):33.

PMID: 36966223 PMC: 10039943. DOI: 10.1038/s41698-023-00370-3.

References

Stylianou S, Clarke R, Brennan K . Aberrant activation of notch signaling in human breast cancer. Cancer Res. 2006; 66(3):1517-25. DOI: 10.1158/0008-5472.CAN-05-3054. View

Gallahan D, Jhappan C, Robinson G, Hennighausen L, Sharp R, Kordon E . Expression of a truncated Int3 gene in developing secretory mammary epithelium specifically retards lobular differentiation resulting in tumorigenesis. Cancer Res. 1996; 56(8):1775-85. View

Song L, Peng Y, Yun J, Rizzo P, Chaturvedi V, Weijzen S . Notch-1 associates with IKKalpha and regulates IKK activity in cervical cancer cells. Oncogene. 2008; 27(44):5833-44. DOI: 10.1038/onc.2008.190. View

Green K, Carroll J . Oestrogen-receptor-mediated transcription and the influence of co-factors and chromatin state. Nat Rev Cancer. 2007; 7(9):713-22. DOI: 10.1038/nrc2211. View

Maier M, Gessler M . Comparative analysis of the human and mouse Hey1 promoter: Hey genes are new Notch target genes. Biochem Biophys Res Commun. 2000; 275(2):652-60. DOI: 10.1006/bbrc.2000.3354. View

Fernandez-Majada V, Aguilera C, Villanueva A, Vilardell F, Robert-Moreno A, Aytes A . Nuclear IKK activity leads to dysregulated notch-dependent gene expression in colorectal cancer. Proc Natl Acad Sci U S A. 2006; 104(1):276-81. PMC: 1765449. DOI: 10.1073/pnas.0606476104. View

Park K, Krishnan V, OMalley B, Yamamoto Y, Gaynor R . Formation of an IKKalpha-dependent transcription complex is required for estrogen receptor-mediated gene activation. Mol Cell. 2005; 18(1):71-82. DOI: 10.1016/j.molcel.2005.03.006. View

Nickoloff B, Osborne B, Miele L . Notch signaling as a therapeutic target in cancer: a new approach to the development of cell fate modifying agents. Oncogene. 2003; 22(42):6598-608. DOI: 10.1038/sj.onc.1206758. View

Reedijk M, Odorcic S, Chang L, Zhang H, Miller N, McCready D . High-level coexpression of JAG1 and NOTCH1 is observed in human breast cancer and is associated with poor overall survival. Cancer Res. 2005; 65(18):8530-7. DOI: 10.1158/0008-5472.CAN-05-1069. View

10.

ElShamy W, Livingston D . Identification of BRCA1-IRIS, a BRCA1 locus product. Nat Cell Biol. 2004; 6(10):954-67. DOI: 10.1038/ncb1171. View

11.

Kato S, Endoh H, Masuhiro Y, Kitamoto T, Uchiyama S, Sasaki H . Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase. Science. 1995; 270(5241):1491-4. DOI: 10.1126/science.270.5241.1491. View

12.

Vooijs M, Schroeter E, Pan Y, Blandford M, Kopan R . Ectodomain shedding and intramembrane cleavage of mammalian Notch proteins is not regulated through oligomerization. J Biol Chem. 2004; 279(49):50864-73. DOI: 10.1074/jbc.M409430200. View

13.

Kiaris H, Politi K, Grimm L, Szabolcs M, Fisher P, Efstratiadis A . Modulation of notch signaling elicits signature tumors and inhibits hras1-induced oncogenesis in the mouse mammary epithelium. Am J Pathol. 2004; 165(2):695-705. PMC: 1618582. DOI: 10.1016/S0002-9440(10)63333-0. View

14.

Cheng P, Zlobin A, Volgina V, Gottipati S, Osborne B, Simel E . Notch-1 regulates NF-kappaB activity in hemopoietic progenitor cells. J Immunol. 2001; 167(8):4458-67. DOI: 10.4049/jimmunol.167.8.4458. View

15.

Neuman E, Ladha M, Lin N, Upton T, Miller S, DiRenzo J . Cyclin D1 stimulation of estrogen receptor transcriptional activity independent of cdk4. Mol Cell Biol. 1997; 17(9):5338-47. PMC: 232384. DOI: 10.1128/MCB.17.9.5338. View

16.

Weng A, Nam Y, Wolfe M, Pear W, Griffin J, Blacklow S . Growth suppression of pre-T acute lymphoblastic leukemia cells by inhibition of notch signaling. Mol Cell Biol. 2003; 23(2):655-64. PMC: 151540. DOI: 10.1128/MCB.23.2.655-664.2003. View

17.

Laganiere J, Deblois G, Lefebvre C, Bataille A, Robert F, Giguere V . From the Cover: Location analysis of estrogen receptor alpha target promoters reveals that FOXA1 defines a domain of the estrogen response. Proc Natl Acad Sci U S A. 2005; 102(33):11651-6. PMC: 1183449. DOI: 10.1073/pnas.0505575102. View

18.

Saint Just Ribeiro M, Hansson M, Wallberg A . A proline repeat domain in the Notch co-activator MAML1 is important for the p300-mediated acetylation of MAML1. Biochem J. 2007; 404(2):289-98. PMC: 1868802. DOI: 10.1042/BJ20061900. View

19.

Rizzo P, Miao H, DSouza G, Osipo C, Song L, Yun J . Cross-talk between notch and the estrogen receptor in breast cancer suggests novel therapeutic approaches. Cancer Res. 2008; 68(13):5226-35. PMC: 4445363. DOI: 10.1158/0008-5472.CAN-07-5744. View

20.

Callahan R, Egan S . Notch signaling in mammary development and oncogenesis. J Mammary Gland Biol Neoplasia. 2004; 9(2):145-63. DOI: 10.1023/B:JOMG.0000037159.63644.81. View