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Overexpression of DAN causes a growth suppression in p53-deficient SAOS-2 cells

E Hanaoka1, T Ozaki, Y Nakamura

  • 1Division of Biochemistry, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuoh-ku, Chiba 260-8717, Japan.

Biochemical and Biophysical Research Communications
|November 10, 2000
PubMed

Insights

Dab (DAN) protein suppresses tumor growth in human bone and soft tissue cancer cells. Secreted Dab acts independently of p53, reducing cell proliferation and drug resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Dab (DAN) and Drm/Gremlin, members of the DAN/Cerberus family, are downregulated in oncogene-transformed rodent fibroblasts.
  • Overexpression of DAN reverses transformed phenotypes in rodent cells.

Purpose of the Study:

  • To investigate the expression of DAN, BMP-2, BMP-4, and BMP receptors (BMPRs) in human bone and soft tissue tumor cell lines.
  • To determine the functional role of DAN in human cancer cell lines, particularly its effect on growth and drug resistance.

Main Methods:

  • Northern blot analysis to detect DAN mRNA expression in five human tumor cell lines.
  • Transient and stable transfection of DAN into SAOS-2 cells (lacking functional p53 and pRB).
  • Assessment of cell growth suppression, p21(Waf1) induction, alkaline phosphatase activity, and drug-resistant colony formation.

Main Results:

  • DAN mRNA was detected in OS-KH and RMS-NK cells, but not in SAOS-2, NOS-1, and ASPS-KY cells.
  • Overexpression of DAN in SAOS-2 cells suppressed growth without inducing p21(Waf1).
  • Overexpression of DAN reduced alkaline phosphatase activity and the number of drug-resistant colonies in SAOS-2 cells.
  • A truncated form of DAN lacking a signal peptide lost its growth-suppressive capability.

Conclusions:

  • The secreted form of DAN exhibits growth-suppressive functions in SAOS-2 cells.
  • Dab's growth suppression in SAOS-2 cells is independent of the p53 pathway.
  • DAN may play a role in regulating drug resistance in certain human cancers.

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