Critical role of estrogen receptor on anoikis and invasion of squamous cell carcinoma

被引:50
作者
Ishida, Hiroyuki
Wada, Koichiro
Masuda, Tomotake
Okura, Masaya
Kohama, Keiko
Sano, Yoshito
Nakajima, Atsushi
Kogo, Mikihiko
Kamisaki, Yoshinori
机构
[1] Osaka Univ, Grad Sch Dent, Dept Pharmacol, Suita, Osaka 5650871, Japan
[2] Osaka Univ, Grad Sch Dent, Dept Maxillofacial Surg 1, Suita, Osaka 5650871, Japan
[3] Yokohama City Univ, Sch Med, Div Gastroenterol, Yokohama, Kanagawa 2360004, Japan
关键词
D O I
10.1111/j.1349-7006.2007.00437.x
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Estrogen receptor (ER) plays an important role in various physiological functions. We examined whether ER alpha and ER beta are expressed in squamous cell carcinoma (SCC), and whether ER is a potential target for antitumor therapy. High-level expression of ER beta, but not ER alpha, was observed in tumor cells of human primary SCC tissues and various SCC cultured cell lines. Treatment with ER antagonist (tamoxifen), but not agonist (estradiol), caused apoptotic cell death of SCC cells in a concentration- and time-dependent manner. Adhesion of SCC was inhibited by the treatment with tamoxifen, but not with estradiol. Tamoxifen reduced the phosphorylation of focal adhesion kinase (FAK), resulting in decreases in phosphorylation of extracellular signal-related kinase (Erk) and mitogen-activated protein kinase. Inhibition of FAK phosphorylation is accompanied by disorder of the cytoskeletal component actin. The cell death caused by tamoxifen is therefore the result of direct interference in cell adhesion, which is called 'anoikis', involving a decrease in intracellular FAK signaling. Expression of epidermal growth factor receptor was also inhibited by treatment with a high concentration of tamoxifen. Knockdown of ER beta by small interfering RNA inhibited the proliferation of SCC. In addition, tamoxifen strongly inhibited invasion of SCC. These results imply a potentially important role for ER, whose inhibition may be effective for the treatment of SCC and the prevention of invasion and metastasis.
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收藏
页码:636 / 643
页数:8
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