The DOI matches its OpenAlex record; 6 of the 6 references it cites were found in a registry or an index.
Hypoxia-Inducible Factor-1 (HIF-1) Up-Regulates Adrenomedullin Expression in Human Tumor Cell Lines during Oxygen Deprivation: A Possible Promotion Mechanism of Carcinogenesis
Open accessAbstract
Little is known about the molecular mechanisms that control adrenomedullin (AM) production in human cancers. We demonstrate here that the expression of AM mRNA in a variety of human tumor cell lines is highly induced in a time-dependent manner by reduced oxygen tension (1% O2) or exposure to hypoxia mimetics such as desferrioxamine mesylate (DFX) or CoCl2. This AM expression seems to be under hypoxia-inducible factor-1 (HIF-1) transcriptional regulation, since HIF-1alpha and HIF-1beta knockout mouse cell lines had an ablated or greatly reduced hypoxia AM mRNA induction. Similarly, inhibition or enhancement of HIF-1 activity in human tumor cells showed an analogous modulation of AM mRNA. Under hypoxic conditions, immunohistochemical analysis of tumor cell lines revealed elevated levels of AM and HIF-1alpha as compared with normoxia, and we also found an increase of immunoreactive AM in the conditioned medium of tumor cells analyzed by RIA. AM mRNA stabilization was shown to be partially responsible for the hypoxic up-regulated expression of AM. In addition, we have identified several putative hypoxia response elements (HREs) in the human AM gene, and reporter studies with selected HREs were capable of enhancing luciferase expression after exposure to DFX. Furthermore, transient coexpression of HIF-1alpha resulted in an augmented transactivation of the reporter gene after DFX treatment. Given that most solid human tumors have focal hypoxic areas and that AM functions as a mitogen, angiogenic factor, and apoptosis-survival factor, our findings implicate the HIF-1/AM link as a possible promotion mechanism of carcinogenesis.
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.
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
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999) · Nature · doi:10.1038/20459 · Cited by 5,180
Cellular and developmental control of O 2 homeostasis by hypoxia-inducible factor 1α
Iyer, N. V., Kotch, L. E., Agani, F., Leung, S. W., Laughner, E., Wenger, R. H., Gassmann, M., Gearhart, J. D., Lawler, A. M., Yu, A. Y., et al. (1998) · Genes & Development · doi:10.1101/gad.12.2.149 · Cited by 2,476
Self-citationHuang, L. E., Gu, J., Schau, M., & Bunn, H. F. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.14.7987 · Cited by 2,113
Maltepe, E., Schmidt, J. V., Baunoch, D., Bradfield, C. A., & Simon, M. C. (1997) · Nature · doi:10.1038/386403a0 · Cited by 781
Oxygen-regulated transferrin expression is mediated by hypoxia-inducible factor-1
Rolfs, A., Kvietikova, I., Gassmann, M., & Wenger, R. H. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.32.20055 · Cited by 401
Self-citationInhibition of hypoxia-inducible factor 1 activity by nitric oxide donors in hypoxia
Sogawa, K., Numayama-Tsuruta, K., Ema, M., Abe, M., Abe, H., & Fujii-Kuriyama, Y. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7368 · Cited by 224
Cited by
The role of myeloid cells in the promotion of tumour angiogenesis
Murdoch, C., Muthana, M., Coffelt, S. B., & Lewis, C. E. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2444 · Cited by 1,642
Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis
Kaur, B., Khwaja, F. W., Severson, E. A., Matheny, S. L., Brat, D. J., & Van Meir, E. G. (2005) · Neuro-Oncology · doi:10.1215/s1152851704001115 · Cited by 725
Bacterial lipopolysaccharide induces HIF-1 activation in human monocytes via p44/42 MAPK and NF-κB
Frede, S., Stockmann, C., Freitag, P., & Fandrey, J. (2006) · Biochemical Journal · doi:10.1042/bj20051839 · Cited by 436
Molecular Biology of Bone Metastasis
Kingsley, L. A., Fournier, P. G. J., Chirgwin, J. M., & Guise, T. A. (2007) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-07-0234 · Cited by 435
Transcriptomic and genomic analysis of human hepatocellular carcinomas and hepatoblastomas†
Luo, J., Ren, B., Keryanov, S., Tseng, G. C., Rao, U. N. M., Monga, S. P., Strom, S., Demetris, A. J., Nalesnik, M., Yu, Y. P., et al. (2006) · Hepatology · doi:10.1002/hep.21328 · Cited by 339
Metadata
- Authors
- Garayoa, M., Martı́nez, A., Lee, S., Pı́o, R., An, W. G., Neckers, L., Trepel, J. B., Montuenga, L. M., Ryan, H. E., Johnson, R. S., Gassmann, M., & Cuttitta, F. F.
- Venue
- Molecular Endocrinology
- Publisher
- Oxford University Press
- Published
- 2000-06-01
- Volume
- 14
- Issue
- 6
- Pages
- 848-862
- ISSN
- 0888-8809 (ISSN-L)
- OpenAlex
- W2123033691
- Cited by
- 262
- References
- 6
- FWCI
- 6.62
- Type
- journal article
- Language
- en
- Open access
- bronze
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
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Hypoxia-Inducible Factor-1 (HIF-1) Up-Regulates Adrenomedullin Expression in Human Tumor Cell Lines during Oxygen Deprivation: A Possible Promotion Mechanism of Carcinogenesis. https://app.cochat.ai/papers/10.1210/me.14.6.848
- The paper
- Garayoa, M., Martı́nez, A., Lee, S., Pı́o, R., An, W. G., Neckers, L., Trepel, J. B., Montuenga, L. M., Ryan, H. E., Johnson, R. S., Gassmann, M., & Cuttitta, F. F. (2000). Hypoxia-Inducible Factor-1 (HIF-1) Up-Regulates Adrenomedullin Expression in Human Tumor Cell Lines during Oxygen Deprivation: A Possible Promotion Mechanism of Carcinogenesis. Molecular Endocrinology. https://doi.org/10.1210/me.14.6.848
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
