ERK signalling in metastatic human MDA-MB-231 breast carcinoma cells is adapted to obtain high urokinase expression and rapid cell proliferation View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1999-08

AUTHORS

Maria Seddighzadeh, Jian-Nian Zhou, Ulrike Kronenwett, Maria C. Shoshan, Gert Auer, Margareta Sten-Linder, Björn Wiman, Stig Linder

ABSTRACT

Increased urokinase plasminogen activator (u-PA) production is associated with tumor invasion and metastasis in several malignancies, including breast cancer. The mechanisms underlying constitutive u-PA expression are not well understood. We examined the relationship between the signal strength of the ERK pathway and the level of u-PA expression in the metastatic human breast cancer cell line MDA-MB-231. Treatment with the MEK1 inhibitor PD98059 resulted in decreased ERK1/2 phosphorylation and decreased u-PA mRNA and protein expression. Inhibition of ERK1/2 activity also led to decreased cell proliferation and to decreased cyclin D1 expression. Less than 5% of total ERK1/2 was phosphorylated in exponentially growing MDA-MB-231 cells, and ERK1/2 activity could be stimulated by okadaic acid. Okadaic acid did not stimulate u-PA expression, but induced strong expression of the cdk-inhibitor p21Cip1. These findings suggest that ERK1/2 signaling is tuned to a level which results in high u-PA expression and rapid cell proliferation. More... »

PAGES

649-654

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1023/a:1006741228402

DOI

http://dx.doi.org/10.1023/a:1006741228402

DIMENSIONS

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10919709


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