Molecular Mechanisms of Mouse Skin Tumor Promotion

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2011 Feb 8

PMID 21297902

Citations 63

Authors

Joyce E Rundhaug

Susan M Fischer

Affiliations

Soon will be listed here.

Abstract

Multiple molecular mechanisms are involved in the promotion of skin carcinogenesis. Induction of sustained proliferation and epidermal hyperplasia by direct activation of mitotic signaling pathways or indirectly in response to chronic wounding and/or inflammation, or due to a block in terminal differentiation or resistance to apoptosis is necessary to allow clonal expansion of initiated cells with DNA mutations to form skin tumors. The mitotic pathways include activation of epidermal growth factor receptor and Ras/Raf/mitogen-activated protein kinase signaling. Chronic inflammation results in inflammatory cell secretion of growth factors and cytokines such as tumor necrosis factor-a and interleukins, as well as production of reactive oxygen species, all of which can stimulate proliferation. Persistent activation of these pathways leads to tumor promotion.

Citing Articles

Effect of narrowband ultraviolet B (311 nm) exposure on skin carcinogenesis in Wistar rats.

Krisanti R, Wanandi S, Wuyung P, Hoemardani A J Adv Vet Anim Res. 2025; 11(4):1105-1113.

PMID: 40013270 PMC: 11855443. DOI: 10.5455/javar.2024.k861.

Zinc oxide nanoparticles derived from Penicillium griseofulvum mitigate DMBA/TPA-promoted mice skin carcinogenesis by modulating NF-ĸB associated signalling.

Li Z, Wu F, Zhang Q Naunyn Schmiedebergs Arch Pharmacol. 2024; 398(1):891-902.

PMID: 39080011 DOI: 10.1007/s00210-024-03311-4.

TFCP2 as a therapeutic nexus: unveiling molecular signatures in cancer.

Kaushik N, Jaiswal A, Bhartiya P, Choi E, Kaushik N Cancer Metastasis Rev. 2024; 43(3):959-975.

PMID: 38451384 DOI: 10.1007/s10555-024-10175-w.

The phenomenon of phototoxicity and long-term risks of commonly prescribed and structurally diverse drugs.

Davis A, Kennelley G, Amaye-Obu T, Jowdy P, Ghadersohi S, Nasir-Moin M J Photochem Photobiol. 2024; 19.

PMID: 38389933 PMC: 10883358. DOI: 10.1016/j.jpap.2023.100221.

NRF3 suppresses squamous carcinogenesis, involving the unfolded protein response regulator HSPA5.

Gurri S, Siegenthaler B, Cangkrama M, Restivo G, Huber M, Saliba J EMBO Mol Med. 2023; 15(11):e17761.

PMID: 37807968 PMC: 10630885. DOI: 10.15252/emmm.202317761.

References

Lee W, Fischer S, Butler A, Locniskar M . Modulation of interleukin-1 alpha mRNA expression in mouse epidermis by tumor promoters and antagonists. Mol Carcinog. 1993; 7(1):26-35. DOI: 10.1002/mc.2940070106. View

Cataisson C, Joseloff E, Murillas R, Wang A, Atwell C, Torgerson S . Activation of cutaneous protein kinase C alpha induces keratinocyte apoptosis and intraepidermal inflammation by independent signaling pathways. J Immunol. 2003; 171(5):2703-13. DOI: 10.4049/jimmunol.171.5.2703. View

Gupta R, DuBois R . Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat Rev Cancer. 2002; 1(1):11-21. DOI: 10.1038/35094017. View

Muller-Decker K, Scholz K, Marks F, Furstenberger G . Differential expression of prostaglandin H synthase isozymes during multistage carcinogenesis in mouse epidermis. Mol Carcinog. 1995; 12(1):31-41. DOI: 10.1002/mc.2940120106. View

Groves R, Mizutani H, Kieffer J, Kupper T . Inflammatory skin disease in transgenic mice that express high levels of interleukin 1 alpha in basal epidermis. Proc Natl Acad Sci U S A. 1995; 92(25):11874-8. PMC: 40505. DOI: 10.1073/pnas.92.25.11874. View

Shoji Y, Takahashi M, Takasuka N, Niho N, Kitamura T, Sato H . Prostaglandin E receptor EP3 deficiency modifies tumor outcome in mouse two-stage skin carcinogenesis. Carcinogenesis. 2005; 26(12):2116-22. DOI: 10.1093/carcin/bgi193. View

Haque S, Sharma P . Interleukins and STAT signaling. Vitam Horm. 2006; 74:165-206. DOI: 10.1016/S0083-6729(06)74007-9. View

Li X, Eckard J, Shah R, Malluck C, Frenkel K . Interleukin-1alpha up-regulation in vivo by a potent carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) and control of DMBA-induced inflammatory responses. Cancer Res. 2002; 62(2):417-23. View

Dempsey E, Newton A, Mochly-Rosen D, Fields A, Reyland M, Insel P . Protein kinase C isozymes and the regulation of diverse cell responses. Am J Physiol Lung Cell Mol Physiol. 2000; 279(3):L429-38. DOI: 10.1152/ajplung.2000.279.3.L429. View

10.

Griner E, Kazanietz M . Protein kinase C and other diacylglycerol effectors in cancer. Nat Rev Cancer. 2007; 7(4):281-94. DOI: 10.1038/nrc2110. View

11.

Fischer S, Patrick K, Lee M, Cameron G . 4 Beta- and 4 alpha-12-O-tetradecanoylphorbol-13-acetate elicit arachidonate release from epidermal cells through different mechanisms. Cancer Res. 1991; 51(3):850-6. View

12.

Rundhaug J, Pavone A, Kim E, Fischer S . The effect of cyclooxygenase-2 overexpression on skin carcinogenesis is context dependent. Mol Carcinog. 2007; 46(12):981-92. DOI: 10.1002/mc.20340. View

13.

Dominey A, Wang X, King Jr L, Nanney L, Gagne T, Sellheyer K . Targeted overexpression of transforming growth factor alpha in the epidermis of transgenic mice elicits hyperplasia, hyperkeratosis, and spontaneous, squamous papillomas. Cell Growth Differ. 1993; 4(12):1071-82. View

14.

Hobbs C, Wei G, Defeo K, Paul B, Hayes C, Gilmour S . Tip60 protein isoforms and altered function in skin and tumors that overexpress ornithine decarboxylase. Cancer Res. 2006; 66(16):8116-22. DOI: 10.1158/0008-5472.CAN-06-0359. View

15.

Wang S, Lien H, Xia W, Chen I, Lo H, Wang Z . Binding at and transactivation of the COX-2 promoter by nuclear tyrosine kinase receptor ErbB-2. Cancer Cell. 2004; 6(3):251-61. DOI: 10.1016/j.ccr.2004.07.012. View

16.

Konger R, Billings S, Thompson A, Morimiya A, Ladenson J, Landt Y . Immunolocalization of low-affinity prostaglandin E receptors, EP and EP, in adult human epidermis. J Invest Dermatol. 2005; 124(5):965-70. DOI: 10.1111/j.0022-202X.2005.23658.x. View

17.

Chida K, Murakami A, Tagawa T, Ikuta T, Kuroki T . Cholesterol sulfate, a second messenger for the eta isoform of protein kinase C, inhibits promotional phase in mouse skin carcinogenesis. Cancer Res. 1995; 55(21):4865-9. View

18.

Konger R, Brouxhon S, Partillo S, VanBuskirk J, Pentland A . The EP3 receptor stimulates ceramide and diacylglycerol release and inhibits growth of primary keratinocytes. Exp Dermatol. 2005; 14(12):914-22. DOI: 10.1111/j.1600-0625.2005.00381.x. View

19.

Hobbs C, Paul B, Gilmour S . Deregulation of polyamine biosynthesis alters intrinsic histone acetyltransferase and deacetylase activities in murine skin and tumors. Cancer Res. 2002; 62(1):67-74. View

20.

Bradham C, Plumpe J, Manns M, Brenner D, Trautwein C . Mechanisms of hepatic toxicity. I. TNF-induced liver injury. Am J Physiol. 1998; 275(3):G387-92. DOI: 10.1152/ajpgi.1998.275.3.G387. View