Dual Inhibition of Both the Epidermal Growth Factor Receptor and erbB2 Effectively Inhibits the Promotion of Skin Tumors during Two-Stage Carcinogenesis

DOI PDF 被引用文献1件 参考文献61件
  • Kaoru Kiguchi
    Authors' Affiliations: 1Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas and 2Division of Pharmacology & Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas
  • Takuya Kitamura
    Authors' Affiliations: 1Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas and 2Division of Pharmacology & Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas
  • Tricia Moore
    Authors' Affiliations: 1Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas and 2Division of Pharmacology & Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas
  • Mohammad Rumi
    Authors' Affiliations: 1Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas and 2Division of Pharmacology & Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas
  • Hsiang-Chun Chang
    Authors' Affiliations: 1Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas and 2Division of Pharmacology & Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas
  • Devon Treece
    Authors' Affiliations: 1Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas and 2Division of Pharmacology & Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas
  • Lynnsie Ruffino
    Authors' Affiliations: 1Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas and 2Division of Pharmacology & Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas
  • Kevin Connolly
    Authors' Affiliations: 1Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas and 2Division of Pharmacology & Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas
  • John DiGiovanni
    Authors' Affiliations: 1Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas and 2Division of Pharmacology & Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas

書誌事項

公開日
2010-08-01
資源種別
journal article
DOI
  • 10.1158/1940-6207.capr-10-0010
公開者
American Association for Cancer Research (AACR)

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説明

<jats:title>Abstract</jats:title> <jats:p>The erbB family of receptor tyrosine kinases are known to play important roles in normal epithelial development and epithelial neoplasia. Considerable evidence also suggests that signaling through the epidermal growth factor receptor (EGFR) plays an important role in multistage skin carcinogenesis in mice; however, less is known about the role of erbB2. In this study, to further examine the role of both erbB2 and EGFR in epithelial carcinogenesis, we examined the effect of a dual erbB2/EGFR tyrosine kinase inhibitor, GW2974, given in the diet on skin tumor promotion during two-stage carcinogenesis in wild-type and BK5.erbB2 mice. In BK5.erbB2 mice, erbB2 is overexpressed in the basal layer of epidermis and leads to heightened sensitivity to skin tumor development. GW2974 effectively inhibited skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in wild-type and BK5.erbB2 mice, although a more marked effect was seen in BK5.erbB2 mice. In addition, this inhibitory effect was reversible when GW2974 treatment was withdrawn. GW2974 inhibited 12-O-tetradecanoylphorbol-13-acetate–induced epidermal hyperproliferation, which correlated with reduced activation of both the EGFR and erbB2. These results support the hypothesis that both the EGFR and erbB2 play an important role in the development of skin tumors during two-stage skin carcinogenesis, especially during the tumor promotion stage. Furthermore, the marked sensitivity of BK5.erbB2 mice to the inhibitory effects of GW2974 during tumor promotion suggest greater efficacy for this compound when erbB2 is overexpressed or amplified as an early event in the carcinogenic process. Cancer Prev Res; 3(8); 940–52. ©2010 AACR.</jats:p>

収録刊行物

  • Cancer Prevention Research

    Cancer Prevention Research 3 (8), 940-952, 2010-08-01

    American Association for Cancer Research (AACR)

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