Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously showed that rasH2 transgenic mice carrying the human c-Ha-ras protooncogene are highly susceptible to chemical skin carcinogenesis. In the dermis of rasH2 mice, mast cells are recruited constitutively, and the number of mast cells increases more than in wild-type mice in response to treatment with 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate. To determine whether enhanced skin tumor development in rasH2 mice is dependent on the recruitment of mast cells, we generated rasH2 KIT(W/Wv) mice by crossing rasH2 mice and W or W(v) KIT mutants, and examined the chemical skin carcinogenesis. In rasH2 KIT(W/Wv) mice, mast cells were not found in the dermis either before or after treatment with 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate. Papilloma multiplicity was up to 4.6-fold higher in rasH2 KIT(+/+) mice compared with their rasH2 KIT(W/Wv) siblings. At 12 weeks after the experiment began, the volumes of tumors were significantly smaller in rasH2 KIT(W/Wv) relative to rasH2 KIT(+/+) mice (rasH2 KIT(W/Wv): 29.2 +/- 19.9 mm(3) versus rasH2 KIT(+/+): 179.6 +/- 726.6 mm(3); P = 0.0153). There was no difference in the latency or multiplicity of papillomas between mice without the rasH2 transgene, KIT(W/Wv) mice and their wild-type littermates. Western blot analysis showed that expression of H-RAS protein in the skin was equivalent in rasH2 KIT(W/Wv) and rasH2 KIT(+/+) mice. In conclusion, the inhibition of c-kit decreased H-ras-induced skin carcinogenesis. The suppression of c-kit may be a unique and effective target as a preclinical model of cancer treatment where the activation of H-ras has a significant role. Targeting mast cells could also be a potential strategy for treating malignancies.
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PMID:Decreased c-kit function inhibits enhanced skin carcinogenesis in c-Ha-ras protooncogene transgenic mice. 1768 12