Anthracyclines activate antiapoptotic phosphorylation in breast cancer.

2004 FEB 5 - (NewsRx.com & NewsRx.net) -- Studies support the ability of anthracyclines to activate antiapoptotic p44/42-MAPK phosphorylation in breast cancer, possibly via the novel mechanism of repression of MKP-1 transcription.

According to recent research from the United States, "Anthracyclines are commonly used chemotherapeutics, and in some models enhance p44/42-mitogen-activated protein kinase (MAPK) pathway signaling by effects on upstream kinases. To evaluate the impact of anthracyclines on p44/42-MAPK in breast cancer, A1N4-myc human mammary and BT-474 and MDA-MB-231 breast carcinoma cells were studied," wrote G.W. Small and colleagues, University of North Carolina, Lineberger Comprehensive Cancer Center.

"Treatment with doxorubicin or epirubicin resulted in increased phospho-p44/42-MAPK levels in a time- and concentration-dependent manner. This was associated with p44/42 activation, as reflected by increased p90 ribosomal protein S6 kinase and Bad phosphorylation. Activation of p44/42 appeared to be antiapoptotic, since MAPK stimulation with epidermal growth factor or a dominant-positive p42 construct inhibited apoptosis," the researchers wrote.

"Modest activation of the upstream MAPK kinase MEK was noted under some conditions, but inhibition of MEK did not abolish p44/42 activation, suggesting a contribution from another mechanism. Anthracyclines were found to decrease expression of MAPK phosphatase-1 (MKP-1) both in vitro and in vivo," the researchers stated.

"MKP-1 mRNA levels were decreased in anthracycline-treated cells, and transcription from the ...