Exp Mol Med.  2002 Mar;34(1):27-31.

Differential modulation of zinc-stimulated p21(Cip/WAF1) and cyclin D1 induction by inhibition of PI3 kinase in HT-29 colorectal cancer cells

• Oh SY
• Park KS
• Kim AJ
• Choi KY

Abstract

Activation of the extra cellular signal regulated kinase (ERK) pathway is involved in both proliferation and growth arrest of cells depending on intensity and duration of stimuli. In this study, we have elucidated differential regulation of the zinc-stimulated p21(CiP/WAF1) and cyclin D1 activation by inhibition of phosphoinositide 3-kinase (PI3K). In HT-29 colorectal cancer cells, the ERK activities were increased by zinc, which was accompanied by the induction of p21(Cip/WAF1) and cyclin D1. However, in the HT-29 cells pre-treated with PI3K inhibitor, LY294002, zinc induced further the p21(CiP/WAF) induction whereas abrogated cyclin D1 induction. In addition, the induction of p21(Cip/WAF1) expression completely inhibited the incorporation of bromodeoxyuridine (BrdU) into the nucleus, indicating that p21(CiP/WAF1) is an important indicator for ERK-dependent growth arrest. These studies suggest presence of an inter-related regulatory mechanism of cell proliferation by ERK and PI3K pathways.

MeSH Terms

1-Phosphatidylinositol 3-Kinase/*metabolism
Chromones/metabolism
Colorectal Neoplasms/*metabolism
Cyclin D1/*metabolism
Cyclins/*metabolism
Enzyme Activation
Enzyme Inhibitors/metabolism
Flavones/metabolism
HT29 Cells
Human
Immunohistochemistry
MAP Kinase Signaling System/physiology
Mitogen-Activated Protein Kinases/metabolism
Morpholines/metabolism
Zinc/*metabolism