Reversible activation of c-Myc in skin: induction of a complex neoplastic phenotype by a single oncogenic lesion - PubMed (original) (raw)
Reversible activation of c-Myc in skin: induction of a complex neoplastic phenotype by a single oncogenic lesion
S Pelengaris et al. Mol Cell. 1999 May.
Free article
Abstract
The protooncogene c-myc regulates cell growth, differentiation, and apoptosis, and its aberrant expression is frequently observed in human cancer. However, the consequences of activating c-Myc in an adult tissue, in which these cellular processes are part of normal homeostasis, remain unknown. In order to achieve this, we have targeted expression of a switchable form of the c-Myc protein to the skin epidermis, a well characterized homeostatic tissue. We show that activation of c-MycER in adult suprabasal epidermis rapidly triggers proliferation and disrupts differentiation of postmitotic keratinocytes. Sustained activation of c-Myc is sufficient to induce papillomatosis together with angiogenesis--changes that resemble hyperplastic actinic keratosis, a commonly observed human precancerous epithelial lesion. All these premalignant changes spontaneously regress upon deactivation of c-MycER.
Similar articles
- Id2 is dispensable for Myc-induced epidermal neoplasia.
Murphy DJ, Swigart LB, Israel MA, Evan GI. Murphy DJ, et al. Mol Cell Biol. 2004 Mar;24(5):2083-90. doi: 10.1128/MCB.24.5.2083-2090.2004. Mol Cell Biol. 2004. PMID: 14966287 Free PMC article. - Defining the temporal requirements for Myc in the progression and maintenance of skin neoplasia.
Flores I, Murphy DJ, Swigart LB, Knies U, Evan GI. Flores I, et al. Oncogene. 2004 Aug 5;23(35):5923-30. doi: 10.1038/sj.onc.1207796. Oncogene. 2004. PMID: 15208685 - Ectopic expression of c-Myc in the skin affects the hair growth cycle and causes an enlargement of the sebaceous gland.
Bull JJ, Pelengaris S, Hendrix S, Chronnell CM, Khan M, Philpott MP. Bull JJ, et al. Br J Dermatol. 2005 Jun;152(6):1125-33. doi: 10.1111/j.1365-2133.2005.06458.x. Br J Dermatol. 2005. PMID: 15948972 - Alterations in epidermal biochemistry as a consequence of stage-specific genetic changes in skin carcinogenesis.
Yuspa SH, Kilkenny A, Cheng C, Roop D, Hennings H, Kruszewski F, Lee E, Strickland J, Greenhalgh DA. Yuspa SH, et al. Environ Health Perspect. 1991 Jun;93:3-10. doi: 10.1289/ehp.91933. Environ Health Perspect. 1991. PMID: 1773799 Free PMC article. Review. - MYC in mammalian epidermis: how can an oncogene stimulate differentiation?
Watt FM, Frye M, Benitah SA. Watt FM, et al. Nat Rev Cancer. 2008 Mar;8(3):234-42. doi: 10.1038/nrc2328. Nat Rev Cancer. 2008. PMID: 18292777 Free PMC article. Review.
Cited by
- Preclinical studies identify non-apoptotic low-level caspase-3 as therapeutic target in pemphigus vulgaris.
Luyet C, Schulze K, Sayar BS, Howald D, Müller EJ, Galichet A. Luyet C, et al. PLoS One. 2015 Mar 6;10(3):e0119809. doi: 10.1371/journal.pone.0119809. eCollection 2015. PLoS One. 2015. PMID: 25748204 Free PMC article. - Genetic and molecular aspects of Helicobacter pylori in gastritis, pre- cancerous conditions and gastric adenocrcinoma.
Shadifar M, Ataee R, Ataie A, Heydari Gorgi AM, Nasri Nasrabadi N, Nouri S. Shadifar M, et al. Gastroenterol Hepatol Bed Bench. 2015 Spring;8(Suppl 1):S15-22. Gastroenterol Hepatol Bed Bench. 2015. PMID: 26171133 Free PMC article. Review. - An "-omycs" Toolbox to Work with MYC.
Whitfield J, Soucek L. Whitfield J, et al. Methods Mol Biol. 2021;2318:1-11. doi: 10.1007/978-1-0716-1476-1_1. Methods Mol Biol. 2021. PMID: 34019283 - Ovol1 regulates the growth arrest of embryonic epidermal progenitor cells and represses c-myc transcription.
Nair M, Teng A, Bilanchone V, Agrawal A, Li B, Dai X. Nair M, et al. J Cell Biol. 2006 Apr 24;173(2):253-64. doi: 10.1083/jcb.200508196. J Cell Biol. 2006. PMID: 16636146 Free PMC article. - Deregulating MYC in a model of HER2+ breast cancer mimics human intertumoral heterogeneity.
Risom T, Wang X, Liang J, Zhang X, Pelz C, Campbell LG, Eng J, Chin K, Farrington C, Narla G, Langer EM, Sun XX, Su Y, Daniel CJ, Dai MS, Löhr CV, Sears RC. Risom T, et al. J Clin Invest. 2020 Jan 2;130(1):231-246. doi: 10.1172/JCI126390. J Clin Invest. 2020. PMID: 31763993 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases