Wnt1 and Wnt5a induce cyclin D1 expression through ErbB1 transactivation in HC11 mammary epithelial cells

EMBO Reports - Tập 4 Số 2 - Trang 166-171 - 2003
Gianluca Civenni1, Thomas Holbro1, Nancy E. Hynes1
1Friedrich Miescher Institute, Maulbeerstrasse 66, CH-4058 Basel, Switzerland

Tóm tắt

Constitutive expression of Wnt1 and Wnt5a in HC11 mammary cells led to elevated TCF transcriptional activity. Intriguingly, Wnt‐expressing cells also displayed activation of ErbB1 and mitogen‐activated protein kinase (MAPK), in contrast to control HC11 cells, which did not. Furthermore, conditioned media harvested from Wnt‐expressing cells stimulated ErbB1 and the MAPK cascade when added to control cells. This process was rapid and could be blocked by an ErbB1 antibody that interferes with ligand binding and by matrix metalloproteinase (MMP) inhibitors. These results suggest that in mammary cells Wnt binding to its receptor, Frizzled (Fz), transactivates ErbB1, probably by MMP‐mediated release of soluble ErbB1 ligands. Importantly, Wnt‐transactivated ErbB1 was responsible for MAPK activation and the increased levels of cyclin D1 present in the Wnt‐expressing HC11 cells. Our finding that Wnts transactivate ErbB1 in addition to stimulating the prototypic β‐catenin/TCF pathway may help to explain why wnt1 is a potent oncogene in the mammary gland.

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Tài liệu tham khảo

Badache A., 2001, Interleukin 6 inhibits proliferation and, in cooperation with an epidermal growth factor receptor autocrine loop, increases migration of T47D breast cancer cells, Cancer Res., 61, 383

10.1016/S0955-0674(98)80013-6

10.1016/S0092-8674(00)00122-7

10.1038/sj.onc.1204709

10.1093/nar/29.7.1410

10.1101/gad.14.6.650

10.1083/jcb.146.4.697

10.1073/pnas.96.11.6235

10.1128/MCB.12.5.2418

10.1038/sj.onc.1204192

10.1126/science.281.5382.1509

10.1128/MCB.10.8.4027

10.1128/MCB.20.9.3210-3223.2000

10.1038/35077108

10.1146/annurev.bi.62.070193.002503

10.1038/sj.onc.1203470

10.1006/dbio.2001.0566

10.1016/S0168-9525(98)01634-5

10.1016/0092-8674(82)90409-3

10.1093/emboj/19.13.3159

10.1101/gad.14.15.1837

10.1038/47260

10.1067/mlc.2000.108753

Taverna D., 1991, EGF receptor, PDGR receptor, and c‐erbB2 receptor activation all promote growth but have distinctive effects upon mouse mammary epithelial cell differentiation, Cell Growth Differ., 2, 145

10.1038/18884

10.1002/med.1022

10.1023/A:1009560330359

10.1038/sj.onc.1204706

10.1074/jbc.275.6.4374

10.1016/S0092-8674(02)01014-0

10.1074/jbc.274.46.33043

10.1186/1471-213X-2-8

10.1038/35082500

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EMBO Reports

Tập 4 Số 2

166-171

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