The DOI matches its Crossref record; 88 of the 88 references it cites were found in a registry or an index.
Placental Transforming Growth Factor-β Is a Downstream Mediator of the Growth Arrest and Apoptotic Response of Tumor Cells to DNA Damage and p53 Overexpression
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Physiological levels of circulating GDF15 are low in healthy humans but increase in disease states and during pregnancy [203] (Table 1).”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [203]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
WAF1, a potential mediator of p53 tumor suppression
El-Deiry, W. S., Tokino, T., Velculescu, V. E., Levy, D. B., Parsons, R., Trent, J. M., Lin, D., Mercer, W. E., Kinzler, K. W., & Vogelstein, B. (1993) · Cell · doi:10.1016/0092-8674(93)90500-p · Cited by 8,321
p53, the cellular gatekeeper for growth and division
Levine, A. J. (1997) · Cell · doi:10.1016/s0092-8674(00)81871-1 · Cited by 7,693
The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.
Wade Harper, J. (1993) · Cell · doi:10.1016/0092-8674(93)90499-g · Cited by 5,651
Lane, D. P. (1992) · Nature · doi:10.1038/358015a0 · Cited by 5,138
Prevention of Apoptosis by Bcl-2: Release of Cytochrome c from Mitochondria Blocked
Yang, J., Liu, X., Bhalla, K. N., Kim, C. N., Ibrado, A. M., Cai, J., Peng, T.-I., Jones, D. P., & Wang, X. (1997) · Science · doi:10.1126/science.275.5303.1129 · Cited by 4,913
Tumor suppressor p53 is a direct transcriptional activator of the human bax gene
Toshiyuki, M., & Reed, J. C. (1995) · Cell · doi:10.1016/0092-8674(95)90412-3 · Cited by 4,063
TGF-β signalling from cell membrane to nucleus through SMAD proteins
Heldin, C., Miyazono, K., & ten Dijke, P. (1997) · Nature · doi:10.1038/37284 · Cited by 3,697
The Transforming Growth Factor-Beta Family
Massagué, J. (1990) · Annual Review of Cell Biology · doi:10.1146/annurev.cb.06.110190.003121 · Cited by 3,041
p53-dependent apoptosis modulates the cytotoxicity of anticancer agents
Lowe, S. W., Ruley, H. E., Jacks, T., & Housman, D. E. (1993) · Cell · doi:10.1016/0092-8674(93)90719-7 · Cited by 2,911
Mutations in the p53 gene occur in diverse human tumour types
Nigro, J. M., Baker, S. J., Preisinger, A. C., Jessup, J. M., Hosteller, R., Cleary, K. R., Signer, S. H., Davidson, N. E., Baylin, S., Devilee, P., et al. (1989) · Nature · doi:10.1038/342705a0 · Cited by 2,730
Research works printed but not linked: 16
- Weichselbaum, 1992, Semin. Oncol., 19, 14
- Miyashita, 1994, Oncogene, 9, 1799
- Fuchs, 1997, Cancer Res., 57, 2550
- Yount, 1999, Cancer Res., 59, 1362
- Brown, 1999, Cancer Res., 59, 1391
- Peled, 1996, Cancer Res., 56, 2148
- Hoodless, 1998, Curr. Topics Microbiol. Immunol., 228, 235
- Chen, 1988, BioTechniques, 6, 632
- Liebermann, 1995, Oncogene, 11, 199
- Nishizaki, 1999, Clin. Cancer Res., 5, 1015
- Meyers, 1993, Mol. Cell. Biol., 13, 6336
- Hahm, 1994, Mol. Cell. Biol., 14, 7111
- Katayose, 1995, Clin. Cancer Res., 1, 889
- Massague, 1996, Cancer Surv., 27, 41
- Schutte, 1996, Cancer Res., 56, 2527
- Frank, 1998, Clin. Cancer Res., 4, 2521
Cited by
Sorted by citations
Cyclooxygenase‐independent actions of cyclooxygenase inhibitors
Tegeder, I., Pfeilschifter, J. M., & Geißlinger, G. (2001) · The FASEB Journal · doi:10.1096/fj.01-0390rev · Cited by 755
Activation of p53 by MEG3 Non-coding RNA
Zhou, Y., Zhong, Y., Wang, Y., Zhang, X., Batista, D. L., Gejman, R., Ansell, P. J., Zhao, J. C., Weng, C., & Klibanski, A. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702029200 · Cited by 665
Members of the heat-shock protein 70 family promote cancer cell growth by distinct mechanismsPreprint
Rohde, M., Daugaard, M., Jensen, M. H., Helin, K., Nylandsted, J., & Jäättelä, M. (2005) · Genes & Development · doi:10.1101/gad.305405 · Cited by 417
Tsai, V. W.-W., Husaini, Y., Sainsbury, A., Brown, D. A., & Breit, S. N. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.07.018 · Cited by 424
Baek, S. J., Kim, K. S., Nixon, J. B., Wilson, L. C., & Eling, T. E. (2001) · Molecular Pharmacology · doi:10.1124/mol.59.4.901 · Cited by 402
Metadata
- Authors
- Li, P.-X., Wong, J., Ayed, A., Ngo, D., Brade, A. M., Arrowsmith, C., Austin, R. C., & Klamut, H. J.
- Affiliations
- University Health Network (CA)
- McMaster University (CA)
- Corresponding author
- Klamut, Henry J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-06
- Volume
- 275
- Issue
- 26
- Pages
- 20127-20135
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2126527070
- Cited by
- 254
- References
- 88
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2022: 3 · 2021: 8 · 2020: 13 · 2019: 10 · 2018: 10 · 2017: 9 · 2016: 6 · 2015: 11 · 2014: 9 · 2013: 10 · 2012: 12
- FWCI
- 3.50
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Medical Research Council Canada
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- TGF-beta superfamily, p53, DNA damage, apoptosis, G1 cell cycle arrest, breast cancer, p53 binding sites, promoter induction, adenoviral overexpression, radiation-induced cell death, chemotherapeutic drug resistance
- MeSH terms
- Adenoviridae, Breast Neoplasms, Cell Cycle, Cell Division, Cell Survival, DNA Damage, Genetic Vectors, Growth Substances, Humans, Pregnancy Proteins, RNA, Messenger, Time Factors, Tissue Distribution, Tumor Cells, Cultured, Blotting, Northern, Transcriptional Activation, Up-Regulation, Genes, p53, Tumor Suppressor Protein p53, Apoptosis, Sequence Analysis, DNA, DNA, Complementary
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
