Differential modulation of zinc-stimulated p21Cip/WAF1 and cyclin D1 induction by inhibition of PI3 kinase in HT-29 colorectal cancer cells

So Young Oh, Ki Sook Park, Jin Ah Kim, Kang Yell Choi

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23 Citations (Scopus)


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 p21Cip/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 p21Cip/WAF1 and cyclin D1. However, in the HT-29 cells pre-treated with PI3K inhibitor, LY294002, zinc induced further the p21Cip/WAF1 induction whereas abrogated cyclin D1 induction. In addition, the induction of p21Cip/WAF1 expression completely inhibited the incorporation of bromodeoxyuridine (BrdU) into the nucleus, indicating that p21Cip/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.

Original languageEnglish
Pages (from-to)27-31
Number of pages5
JournalExperimental and Molecular Medicine
Issue number1
Publication statusPublished - 2002 Mar 31

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry


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