Placental transforming growth factor-beta is a downstream mediator of the growth arrest and apoptotic response of tumor cells to DNA damage and p53 overexpression - PubMed (original) (raw)

. 2000 Jun 30;275(26):20127-35.

doi: 10.1074/jbc.M909580199.

Affiliations

• PMID: 10777512
• DOI: 10.1074/jbc.M909580199

Free article

Placental transforming growth factor-beta is a downstream mediator of the growth arrest and apoptotic response of tumor cells to DNA damage and p53 overexpression

P X Li et al. J Biol Chem. 2000.

Free article

Abstract

The p53 tumor suppressor gene and members of the transforming growth factor-beta (TGF-beta) superfamily play central roles in signaling cell cycle arrest and apoptosis (programmed cell death) in normal development and differentiation, as well as in carcinogenesis. Here we describe a distantly related member of the TGF-beta superfamily, designated placental TGF-beta (PTGF-beta), that is up-regulated in response to both p53-dependent and -independent apoptotic signaling events arising from DNA damage in human breast cancer cells. PTGF-beta is normally expressed in placenta and at lower levels in kidney, lung, pancreas, and muscle but could not be detected in any tumor cell line studied. The PTGF-beta promoter is activated by p53 and contains two p53 binding site motifs. Functional studies demonstrated that one of these p53 binding sites is essential for p53-mediated PTGF-beta promoter induction and specifically binds recombinant p53 in gel mobility shift assays. PTGF-beta overexpression from a recombinant adenoviral vector (AdPTGF-beta) led to an 80% reduction in MDA-MB-468 breast cancer cell viability and a 50-60% reduction in other human breast cancer cell lines studied, including MCF-7 cells, which are resistant to growth inhibition by recombinant wild-type p53. Like p53, PTGF-beta overexpression was seen to induce both G(1) cell cycle arrest and apoptosis in breast tumor cells. These results provide the first evidence for a direct functional link between p53 and the TGF-beta superfamily and implicate PTGF-beta as an important intercellular mediator of p53 function and the cytostatic effects of radiation and chemotherapeutic cancer agents.

PubMed Disclaimer

Similar articles

• PTGF-beta, a type beta transforming growth factor (TGF-beta) superfamily member, is a p53 target gene that inhibits tumor cell growth via TGF-beta signaling pathway.
  Tan M, Wang Y, Guan K, Sun Y. Tan M, et al. Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):109-14. doi: 10.1073/pnas.97.1.109. Proc Natl Acad Sci U S A. 2000. PMID: 10618379 Free PMC article.
• Convergence of p53 and TGF-beta signaling networks.
  Dupont S, Zacchigna L, Adorno M, Soligo S, Volpin D, Piccolo S, Cordenonsi M. Dupont S, et al. Cancer Lett. 2004 Sep 30;213(2):129-38. doi: 10.1016/j.canlet.2004.06.008. Cancer Lett. 2004. PMID: 15327827 Review.
• New insights into p53 activation.
  Brooks CL, Gu W. Brooks CL, et al. Cell Res. 2010 Jun;20(6):614-21. doi: 10.1038/cr.2010.53. Epub 2010 Apr 20. Cell Res. 2010. PMID: 20404858 Free PMC article. Review.

Cited by

• Growth differentiation factor-15 may be a novel biomarker in pancreatic cancer: A review.
  Guo M, Zhao H. Guo M, et al. Medicine (Baltimore). 2024 Feb 9;103(6):e36594. doi: 10.1097/MD.0000000000036594. Medicine (Baltimore). 2024. PMID: 38335385 Free PMC article. Review.
• Macrophage inhibitory cytokine-1 in cancer: Beyond the cellular phenotype.
  Muniyan S, Pothuraju R, Seshacharyulu P, Batra SK. Muniyan S, et al. Cancer Lett. 2022 Jun 28;536:215664. doi: 10.1016/j.canlet.2022.215664. Epub 2022 Mar 26. Cancer Lett. 2022. PMID: 35351601 Free PMC article. Review.
• The Role of GDF15 as a Myomitokine.
  Johann K, Kleinert M, Klaus S. Johann K, et al. Cells. 2021 Nov 3;10(11):2990. doi: 10.3390/cells10112990. Cells. 2021. PMID: 34831213 Free PMC article. Review.
• Mechanism of sensitivity to cisplatin, docetaxel, and 5-fluorouracil chemoagents and potential erbB2 alternatives in oral cancer with growth differentiation factor 15 overexpression.
  Zhao TC, Zhou ZH, Ju WT, Liang SY, Tang X, Zhu DW, Zhang ZY, Zhong LP. Zhao TC, et al. Cancer Sci. 2022 Feb;113(2):478-488. doi: 10.1111/cas.15218. Epub 2021 Dec 20. Cancer Sci. 2022. PMID: 34826159 Free PMC article.
• Emerging roles of growth differentiation factor-15 in brain disorders (Review).
  Jiang WW, Zhang ZZ, He PP, Jiang LP, Chen JZ, Zhang XT, Hu M, Zhang YK, Ouyang XP. Jiang WW, et al. Exp Ther Med. 2021 Nov;22(5):1270. doi: 10.3892/etm.2021.10705. Epub 2021 Sep 7. Exp Ther Med. 2021. PMID: 34594407 Free PMC article. Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations

• Molecular Biology Databases

  • BioCyc

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal