RGD Reference Report - Proteomic and pathway analyses reveal a network of inflammatory genes associated with differences in skin tumor promotion susceptibility in DBA/2 and C57BL/6 mice. - Rat Genome Database

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Proteomic and pathway analyses reveal a network of inflammatory genes associated with differences in skin tumor promotion susceptibility in DBA/2 and C57BL/6 mice.

Authors: Shen, J  Abel, EL  Riggs, PK  Repass, J  Hensley, SC  Schroeder, LJ  Temple, A  Chau, A  McClellan, SA  Rho, O  Kiguchi, K  Ward, MD  Semmes, OJ  Person, MD  Angel, JM  DiGiovanni, J 
Citation: Shen J, etal., Carcinogenesis. 2012 Nov;33(11):2208-19. doi: 10.1093/carcin/bgs213. Epub 2012 Jul 10.
RGD ID: 7421558
Pubmed: PMID:22782996   (View Abstract at PubMed)
PMCID: PMC3483013   (View Article at PubMed Central)
DOI: DOI:10.1093/carcin/bgs213   (Journal Full-text)

Genetic susceptibility to two-stage skin carcinogenesis is known to vary significantly among different stocks and strains of mice. In an effort to identify specific protein changes or altered signaling pathways associated with skin tumor promotion susceptibility, a proteomic approach was used to examine and identify proteins that were differentially expressed in epidermis between promotion-sensitive DBA/2 and promotion-resistant C57BL/6 mice following treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). We identified 19 differentially expressed proteins of which 5 were the calcium-binding proteins annexin A1, parvalbumin alpha, S100A8, S100A9, and S100A11. Further analyses revealed that S100A8 and S100A9 protein levels were also similarly differentially upregulated in epidermis of DBA/2 versus C57BL/6 mice following topical treatment with two other skin tumor promoters, okadaic acid and chrysarobin. Pathway analysis of all 19 identified proteins from the present study suggested that these proteins were components of several networks that included inflammation-associated proteins known to be involved in skin tumor promotion (e.g. TNF-alpha, NFkappaB). Follow-up studies revealed that Tnf, Nfkb1, Il22, Il1b, Cxcl1, Cxcl2 and Cxcl5 mRNAs were highly expressed in epidermis of DBA/2 compared with C57BL/6 mice at 24h following treatment with TPA. Furthermore, NFkappaB (p65) was also highly activated at the same time point (as measured by phosphorylation at ser276) in epidermis of DBA/2 mice compared with C57BL/6 mice. Taken together, the present data suggest that differential expression of genes involved in inflammatory pathways in epidermis may play a key role in genetic differences in susceptibility to skin tumor promotion in DBA/2 and C57BL/6 mice.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Skin Neoplasms  ISOAnxa1 (Mus musculus)7421558; 7421558 RGD 
Skin Neoplasms  IEP 7421558 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Anxa1  (annexin A1)

Genes (Mus musculus)
Anxa1  (annexin A1)

Genes (Homo sapiens)
ANXA1  (annexin A1)


Additional Information