Density-dependent ERK MAPK expression regulates MMP-9 and influences growth
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Previous work has shown that expression of the extracellular signal-regulated kinase (ERK) is decreased by high density in normal fibroblast cells, and this was correlated with increased expression of mitogen-activated protein kinase phosphatases. Because of these differences in ERK regulation upon contact inhibition, it is likely that other cellular responses may be influenced by the attainment of a contact-inhibited state. Expression of matrix metalloproteinase-9 and cadherin cleavage were both found to be decreased upon reaching high culture density. Inhibition of ERK activity with the MEK inhibitor PD98059 resulted in increased expression of cadherins, while constitutive activation of ERK through the use of expression of an ERK construct with a D319N sevenmaker mutation resulted in decreased expression of cadherins and enhanced colony formation of HT-1080 fibrosarcoma cells. Taken together, these results corroborate a role for the regulation of ERK upon the attainment of a contact-inhibited state with increased expression of cadherins.
KeywordsMMP-9 Contact inhibition ERK Cadherin
We wish to thank Afroditi Emporelli, Allison Pass, Mena Gaballah, Kaveri Kaushal, Megan Hodges, and Monali Patel for technical assistance. This work was supported by Grant R15GM076076 from the National Institute of General Medical Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences or the National Institutes of Health. Additional summer support for P. Patel was provided by the Monmouth University School of Science and the Independent College Fund of New Jersey (ICFNJ).
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