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Mutation of the PI3' kinase gene in a human colon carcinoma cell line, HCC2998

Bin-Hi Shi1, Takeshi Nashimoto, Ryota Andoh

  • 1Laboratory of Biological Chemistry, Division of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan.

DNA and Cell Biology
|July 20, 2006
PubMed

Insights

Mutations in the p85alpha gene of HCC2998 colon cancer cells create aberrant proteins. This may lead to cell dedifferentiation through an autocrine loop involving phosphatidylinositol 3-kinase (PI3K) and ErbB3.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • HCC2998 cells, a human colon carcinoma line, dedifferentiate upon expression of active phosphatidylinositol 3-kinase (PI3K).
  • These cells exhibit low levels of aberrant p85alpha regulatory subunit sizes (50 and 76 kDa).

Purpose of the Study:

  • To investigate the genetic basis for the aberrant p85alpha expression in HCC2998 cells.
  • To explore the functional consequences of wild-type p85alpha introduction and potential autocrine signaling in colon cancer dedifferentiation.

Main Methods:

  • DNA sequencing of the p85alpha gene in HCC2998 cells.
  • Introduction of wild-type p85alpha into HCC2998 cells.
  • Analysis of cell morphology, mucin secretion, and ErbB3 phosphorylation.

Main Results:

  • Identified independent point mutations in both alleles of the p85alpha gene, affecting coding and splicing sequences, leading to aberrant protein forms.
  • Introduction of wild-type p85alpha caused minor cell rounding and increased mucin secretion.
  • Observed tyrosine phosphorylation of ErbB3, which subsequently bound to PI3K, suggesting activation of an autocrine loop.

Conclusions:

  • Point mutations in both p85alpha alleles explain the expression of aberrant proteins in HCC2998 cells.
  • ErbB3 activation upstream of PI3K suggests an autocrine loop contributing to colon cancer cell dedifferentiation.

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