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The BMP signaling pathway leads to enhanced proliferation in serous ovarian cancer-A potential therapeutic target.

Publication ,  Journal Article
Peng, J; Yoshioka, Y; Mandai, M; Matsumura, N; Baba, T; Yamaguchi, K; Hamanishi, J; Kharma, B; Murakami, R; Abiko, K; Murphy, SK; Konishi, I
Published in: Mol Carcinog
April 2016

Members of the transforming growth factor-β (TGF-β) superfamily transduce signals via SMAD proteins. SMAD2 and SMAD3 mediate TGF-β signaling, whereas SMAD1, SMAD5, and SMAD8/9 transduce bone morphogenetic protein (BMP) signals. We would like to identify the function of BMP/SMAD5 signaling in serous ovarian cancer. The protein levels of total SMAD5 and phosphorylated SMAD5 (pSMAD5) were examined by immunohistochemical analysis using clinical serous ovarian cancer samples. Following treatment with either recombinant BMP2 (rBMP2) or Dorsomorphin (DM), western blotting was performed to observe pSMAD5 protein in the cytoplasm and the nucleus, separately. Cell proliferation was detected in SMAD5 knockdown serous ovarian cancer cell lines cultured with DM or rBMP2. The impact of DM or rBMP2 on tumor growth was observed in a mouse model of serous ovarian cancer. An inverse correlation was observed between pSMAD5 levels in the nucleus and the prognosis of patients with serous ovarian cancer. The treatment of SK-OV-3 with rBMP2 stimulated pSMAD5 translocation from the cytoplasm to the nucleus, and the addition of DM inhibited this effect. The proliferation of ovarian cancer cell lines was enhanced by BMP2 and suppressed by DM via SMAD5 in vitro. In vitro and in vivo experiments clearly demonstrated BMP2-stimulated proliferation of serous ovarian cancer and inhibition of this effect by DM. Our data suggests that BMP/SMAD5 signaling plays an important role and, therefore, becomes a potential therapeutic target in serous ovarian cancer. © 2015 Wiley Periodicals, Inc.

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Published In

Mol Carcinog

DOI

EISSN

1098-2744

Publication Date

April 2016

Volume

55

Issue

4

Start / End Page

335 / 345

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Smad5 Protein
  • Signal Transduction
  • Recombinant Proteins
  • Pyrimidines
  • Pyrazoles
  • Protein Kinase Inhibitors
  • Prognosis
  • Phosphorylation
  • Ovary
 

Citation

APA
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Peng, J., Yoshioka, Y., Mandai, M., Matsumura, N., Baba, T., Yamaguchi, K., … Konishi, I. (2016). The BMP signaling pathway leads to enhanced proliferation in serous ovarian cancer-A potential therapeutic target. Mol Carcinog, 55(4), 335–345. https://doi.org/10.1002/mc.22283
Peng, Jin, Yumiko Yoshioka, Masaki Mandai, Noriomi Matsumura, Tsukasa Baba, Ken Yamaguchi, Junzo Hamanishi, et al. “The BMP signaling pathway leads to enhanced proliferation in serous ovarian cancer-A potential therapeutic target.Mol Carcinog 55, no. 4 (April 2016): 335–45. https://doi.org/10.1002/mc.22283.
Peng J, Yoshioka Y, Mandai M, Matsumura N, Baba T, Yamaguchi K, et al. The BMP signaling pathway leads to enhanced proliferation in serous ovarian cancer-A potential therapeutic target. Mol Carcinog. 2016 Apr;55(4):335–45.
Peng, Jin, et al. “The BMP signaling pathway leads to enhanced proliferation in serous ovarian cancer-A potential therapeutic target.Mol Carcinog, vol. 55, no. 4, Apr. 2016, pp. 335–45. Pubmed, doi:10.1002/mc.22283.
Peng J, Yoshioka Y, Mandai M, Matsumura N, Baba T, Yamaguchi K, Hamanishi J, Kharma B, Murakami R, Abiko K, Murphy SK, Konishi I. The BMP signaling pathway leads to enhanced proliferation in serous ovarian cancer-A potential therapeutic target. Mol Carcinog. 2016 Apr;55(4):335–345.
Journal cover image

Published In

Mol Carcinog

DOI

EISSN

1098-2744

Publication Date

April 2016

Volume

55

Issue

4

Start / End Page

335 / 345

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Smad5 Protein
  • Signal Transduction
  • Recombinant Proteins
  • Pyrimidines
  • Pyrazoles
  • Protein Kinase Inhibitors
  • Prognosis
  • Phosphorylation
  • Ovary