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Isolation of a novel mouse variant of the drs tumor suppressor gene

Takao Kawai1, Yasuhiko Suzuki, Atsuko Yamashita

  • 1Division of Food Microbiology, Osaka Prefectural Institute of Public Health, Nakamichi, Higashinari-ku, 537-0025, Osaka, Japan.

Cancer Letters
|June 7, 2002
PubMed

Insights

The drs gene suppresses cancer growth by inhibiting anchorage-independent growth. A variant with fewer consensus repeats (CRs) is critical for this tumor suppressor function.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • The drs gene functions as a transformation suppressor against the v-src oncogene.
  • Drs protein possesses a transmembrane domain and three Sushi motifs (CRs) in its extracellular region.
  • The drs gene can suppress anchorage-independent growth in human cancer cell lines.

Purpose of the Study:

  • To report the isolation of a novel variant cDNA of mouse drs (mDRS-2) with two CRs.
  • To characterize a mouse homolog of drs (mDRS-1) with three CRs.
  • To investigate the tumor suppressor function of these mouse drs (mDRS) cDNAs in human cancer cells.

Main Methods:

  • Isolation of novel mouse drs (mDRS) variant cDNAs.
  • Expression of mDRS-1 and mDRS-2 in human cancer cell lines.
  • Assessment of anchorage-independent growth suppression.

Main Results:

  • Isolation of mDRS-1 (three CRs) and mDRS-2 (two CRs).
  • Both mDRS-1 and mDRS-2 demonstrated suppressor functions in human cancer cells.
  • The absence of one CR in mDRS-2 was found to be critical for suppressing anchorage-independent growth.

Conclusions:

  • The number of CRs in drs protein influences its tumor suppressor activity.
  • A reduction in CRs is essential for the suppression of anchorage-independent growth.
  • Drs variants may offer new therapeutic targets for cancer treatment.

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