Differential ErbB1 signaling in squamous cell versus basal cell carcinoma of the skin

被引:69
作者
Rittie, Laure
Kansra, Sanjay
Stoll, Stefan W.
Li, Yong
Gudjonsson, Johann E.
Shao, Yuan
Michael, Lowell E.
Fisher, Gary J.
Johnson, Timothy M.
Elder, James T.
机构
[1] Univ Michigan, Dept Dermatol, Med Ctr, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Dept Otolaryngol, Med Ctr, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Dept Surg, Med Ctr, Ann Arbor, MI 48109 USA
[4] Univ Michigan, Dept Radiat Oncol, Med Ctr, Ann Arbor, MI 48109 USA
[5] Ann Arbor Vet Affairs Hlth Syst, Ann Arbor, MI USA
关键词
D O I
10.2353/ajpath.2007.060537
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
in this study, we examined ErbB1 signaling in human basal and squamous cell carcinomas (BCC and SCC) of the skin in vivo. We used enzyme-linked immunosorbent assay, laser capture microdissection-coupled real-time reverse transcriptase-polymerase chain reaction, and immunohistochemistry to assess expression and activation levels of ErbB1 protein, ligands, and potential downstream effectors, in BCC and SCC tumors, stroma, and adjacent epidermis. Although total ErbB1 protein and mRNA were similar in cancerous and normal skin, we found that ErbB1 activation (phospho-Tyr(1068)) was greater in bulk SCC versus BCC or normal skin. in addition, three ErbB1 ligand transcripts (amphiregulin, heparin-binding epidermal growth factor-like growth factor, and transforming growth factor-a) were up-regulated in tumor cells of SCC but not BCC. Expression of these ligands was also increased in asymptomatic epidermis adjacent to both SCC and BCC, relative to normal skin. Interestingly, betacellulin transcript levels were inversely regulated compared with the other ligands. Consistently, downstream ErbB1 effectors (Erk1/2 and Akt) were activated in tumor cells of SCC but not of BCC and in adjacent epidermis of both BCC and SCC. These results demonstrate that ErbB1 signaling is hyperactive in tumor cells of SCC but not of BCC and in nearby asymptomatic epidermis of both tumor types. Our results suggest that targeting ErbB1 signaling might be of benefit in the treatment of SCC.
引用
收藏
页码:2089 / 2099
页数:11
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