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Upregulation of the KIAA1199 gene is associated with cellular mortality

Eriko Michishita1, Giannina Garcés, J Carl Barrett

  • 1Laboratory of Biosystems and Cancer, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bldg. 37, Rm. 5046, MSC-4264, Bethesda, MD 20892, USA.

Cancer Letters
|September 15, 2005
PubMed

Insights

Transferring chromosome 3 induces cellular senescence in cancer cells. The KIAA1199 gene is upregulated in these mortal cells, suggesting its role in suppressing cancer cell immortalization.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Normal human chromosome 3 transfer induces senescence in immortal renal cell carcinoma (RCC) cells.
  • Identifying genes involved in chromosome 3-induced cellular mortality is crucial for understanding cancer suppression.
  • Previous cDNA subtraction identified differentially expressed genes between immortal RCC cells and their mortal counterparts.

Purpose of the Study:

  • To clone and characterize KIAA1199, a differentially expressed gene identified in chromosome 3-induced senescence.
  • To investigate the expression patterns of KIAA1199 in various cellular contexts and human tissues.

Main Methods:

  • cDNA subtraction hybridization
  • cDNA cloning and characterization
  • Northern blot analysis
  • Reverse transcription polymerase chain reaction (RT-PCR)

Main Results:

  • KIAA1199 mRNA is significantly upregulated in mortal RCC cells (RCC23+3) compared to immortal RCC cells (RCC23).
  • KIAA1199 mRNA expression shows no significant change during replicative aging in normal human cells.
  • Immortalized cell lines (fibroblasts, breast cancer) exhibit lower KIAA1199 mRNA levels than their normal counterparts.
  • KIAA1199 mRNA is widely expressed in normal human tissues, with the highest levels in the brain.
  • The KIAA1199 gene is located on chromosome 15q25, a region containing a mapped brain tumor suppressor gene.

Conclusions:

  • KIAA1199 is upregulated in response to chromosome 3-induced senescence, indicating its potential role in cellular mortality.
  • KIAA1199 expression is inversely correlated with cellular immortalization in cancer and fibroblast cell lines.
  • These findings suggest KIAA1199 may function as a tumor suppressor by promoting cellular mortality and inhibiting carcinogenesis.

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