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Attenuation of p38 MAPK activity upon contact inhibition in fibroblasts

Michael Slisz1, Emily Rothenberger, Dorothy Hutter

  • 1Department of Biology, Monmouth University, 400 Cedar Avenue, West Long Branch, NJ 07764, USA.

Molecular and Cellular Biochemistry
|October 2, 2007
PubMed

Insights

Contact inhibition, a crucial cell growth control mechanism, involves the negative regulation of p38 signaling. This pathway

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Contact inhibition is a key regulator of normal cell growth.
  • Mitogen-activated protein kinase phosphatases (MKPs) increase with contact inhibition, reducing ERK activity.
  • The roles of p38 and JNK in contact inhibition remain unclear.

Purpose of the Study:

  • To investigate the involvement of p38 and JNK signaling pathways in the transition to contact inhibition.
  • To compare these pathways in normal fibroblasts versus fibrosarcoma cells lacking contact inhibition.

Main Methods:

  • Normal human fibroblasts (BJ) and HT-1080 fibrosarcoma cells were cultured to varying densities.
  • Assays were performed to measure total levels and phosphorylation states of p38 and JNK.
  • Overexpression studies of MKP-1 and a phosphatase-resistant p38 mutant were conducted.

Main Results:

  • p38 was active in proliferating cells but attenuated in contact-inhibited normal fibroblasts, unlike fibrosarcoma cells.
  • JNK activation was not observed.
  • Downstream transcription factor ATF-2 activation was reduced upon contact inhibition.
  • MKP-1 overexpression reduced proliferation; p38(N316) enhanced proliferation in normal fibroblasts.

Conclusions:

  • Negative regulation of p38 signaling is implicated in contact-inhibited growth control.
  • p38 pathway modulation affects cell proliferation and contact inhibition.
  • Findings suggest p38 as a potential target for cancer therapeutics.

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