ArticleOncogene1999
MDM2 overexpression generates a skin phenotype in both wild type and p53 null mice.
Article in Oncogene, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- Experimental Models for the Study of Hereditary Cornification Defects.Biomedicines · 2021Review
- MDM2 and mitochondrial function: One complex intersection.Biochemical pharmacology · 2019Review
- Human neonatal stem cell-derived skin substitute improves healing of severe burn wounds in a rat model.Cell biology international · 2019Article
- Article
- A novel microdeletion in LOR causing autosomal dominant loricrin keratoderma.The British journal of dermatology · 2015Article
- In Vitro Differentiation Potential of Human Placenta Derived Cells into Skin Cells.Stem cells international · 2015Article
- Identifying a hyperkeratosis signature in autosomal recessive congenital ichthyosis: Mdm2 inhibition prevents hyperkeratosis in a rat ARCI model.The Journal of investigative dermatology · 2014Article
- Molecular pathways: targeting Mdm2 and Mdm4 in cancer therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Review
- The mysterious human epidermal cell cycle, or an oncogene-induced differentiation checkpoint.Cell cycle (Georgetown, Tex.) · 2012Review
- A novel regulation of VEGF expression by HIF-1α and STAT3 in HDM2 transfected prostate cancer cells.Journal of cellular and molecular medicine · 2012Article
- Natural product MDM2 inhibitors: anticancer activity and mechanisms of action.Current medicinal chemistry · 2012Review
- A mitosis block links active cell cycle with human epidermal differentiation and results in endoreplication.PloS one · 2010Article
- A functional SNP in the MDM2 promoter, pigmentary phenotypes, and risk of skin cancer.Cancer causes & control : CCC · 2009Article
- The RING finger domain of MDM2 is essential for MDM2-mediated TGF-beta resistance.Molecular biology of the cell · 2007Article
- A small nuclear RNA, hdm365, is the major processing product of the human mdm2 gene.Nucleic acids research · 2003Article
- Article
- The mdm2 proto-oncogene sensitizes human medullary thyroid carcinoma cells to ionizing radiation.Oncogene · 2002Article
- MDM2 induces hyperplasia and premalignant lesions when expressed in the basal layer of the epidermis.The EMBO journal · 2000Article
- Article
- Switch from p53 to MDM2 as differentiating human keratinocytes lose their proliferative potential and increase in cellular size.Oncogene · 2000Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The MDM2 proto-oncogene is overexpressed in human tumours and regulates the activities of the tumour suppressors p53 and pRB. We created mice that overexpress MDM2 under the control of the CMV promoter. These mice did not display an increased tumour incidence, but rather a specific skin phenotype, characterized by desquamation and hyperkeratosis. Transgenic MDM2 was found to be overexpressed in the epidermis, a tissue that normally expresses high levels of MDM2. The phenotype appeared during the first week after birth and then lessened with age, closely following the level of expression of the transgene. MDM2 overexpression was associated with an increase in proliferation in the basal layer, thickening of the epidermis, altered expression of the differentiation markers cytokeratin CK14, CK10 and CK1, and a decrease in the size and the number of granules that contain products of differentiation. Transgenic mice on a p53 null background displayed similar although not identical changes, showing that the effects of MDM2 are to a certain degree p53 independent. The skin is a major site of MDM2 expression in mice, raising the possibility that MDM2 overexpression perturbs the normal pattern of MDM2 expression and inhibits differentiation of the epidermis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.