Use of a TGFbeta type I receptor inhibitor in mouse skin carcinogenesis reveals a dual role for TGFbeta signaling in tumor promotion and progression.

ABSTRACT: Pharmacological inhibitors of the transforming growth factor β (TGFβ) type I receptor (ALK5) have shown promise in blocking growth of xenotransplanted cancer cell lines but the effect on a multistage cancer model is not known. To test this, we treated mouse skin with SB431542 (SB), a well-characterized ALK5 inhibitor, during a two-stage skin carcinogenesis assay. Topical SB significantly reduced the total number, incidence and size of papillomas compared with 12-O-tetradecanoylphorbol 13-acetate (TPA) promotion alone, and this was linked to increased epidermal apoptosis, decreased proliferation and decreased cutaneous inflammation during promotion. In contrast, the frequency of conversion to squamous cell carcinoma (SCC) was 2-fold higher in papillomas treated with SB. Although there was n

SUBMITTER: Mordasky Markell L 

PROVIDER: S-EPMC2994279 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature