Implications of EGFR inhibition in ovarian cancer cell proliferation
Implications of EGFR inhibition in ovarian cancer cell proliferation
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DOI：
10.1016/j.ygyno.2008.02.030
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发表时间：
2008-06-01
影响因子：
4.7
通讯作者：
Lea, Jayanthi S.
中科院分区：
文献类型：
--
作者：
Phelps, Shawna L. Bull;Schorge, John O.;Lea, Jayanthi S.
目标.表皮生长因子受体（埃格）是人表皮受体（HER）家族的四个成员之一，在多种恶性肿瘤中过度表达。EGFR在卵巢癌中的过度表达与预后不良相关。通过其酪氨酸激酶结构域靶向抑制EGFR是肺癌的成功治疗。我们的目的是将表皮生长因子受体抑制剂在卵巢癌中的过度表达和生长抑制联系起来。Western blot检测HER在9个卵巢癌细胞系和1个肺癌细胞系中的表达。分析EGFR磷酸化位点并进行DNA测序。在酪氨酸激酶抑制剂吉非替尼和EGFR单克隆抗体西妥昔单抗存在下进行细胞增殖测定。测定50%这些疗法的抑制浓度，并在所有细胞系中进行比较。以肺癌细胞系HCC 827为对照。9个卵巢癌细胞系和对照肺癌细胞系中有4个（44%）表达EGFR。这些相同的细胞系在位置992处显示出共同的磷酸化残基，而其他残基被磷酸化。除一个细胞系外，所有细胞系均表达至少一个HER家族成员。卵巢癌细胞系的突变分析显示EGFR外显子18-21没有突变。使用吉非替尼和西妥昔单抗的细胞增殖试验显示，与对照HCC 827相比，卵巢癌细胞系中的反应最小，但与没有HER家族表达的一种细胞系相比相对敏感。卵巢癌细胞系显示活化EGFR的可变表达。在缺乏酪氨酸激酶突变或过度表达EGFR的卵巢肿瘤中，单独抑制EGFR不太可能导致临床反应。爱思唯尔公司出版
Objectives. Epidermal Growth Factor Receptor (EGER) is one of the four members of the Human Epidermal Receptor (HER) family and is over-expressed in multiple malignancies. EGFR over-expression in ovarian cancer has been associated with poor prognosis. Targeted inhibition of EGFR via its tyrosine kinase domain is a successful treatment in lung cancer. Our objective was to correlate EGFR over-expression and growth inhibition, by EGF receptor inhibitors, in ovarian cancer.Materials and methods. HER expression in nine epithelial ovarian cancer cell lines and one lung cancer cell line was determined by Western blot analysis. EGFR phosphorylation sites were analyzed and DNA sequencing was per-formed. Cell proliferation assays were performed in the presence of the tyrosine kinase inhibitor, gefitinib, and the EGFR monoclonal antibody, cetuximab. Inhibitory concentrations of 50% of these therapies were determined and compared across all cell lines. The lung cancer cell line, HCC827, was used as a control.Results. Four of nine (44%) ovarian cancer cell lines and the control lung cancer cell line expressed EGFR. These same cell lines showed a common phosphorylated residue at position 992, while other residues were variably phosphorylated. All but one cell line expressed at least one HER family member. Mutational analysis of the ovarian cancer cell lines showed no mutations in EGFR exons 18-21. Cell proliferation assays using gefitinib and cetuximab showed minimal response in the ovarian cancer cell lines when compared to the control HCC827, but relative sensitivity compared to the one cell line that had no HER family expression.Conclusions. Ovarian cancer cell lines show variable expression of activated EGFR. EGFR inhibition alone, in ovarian rumors that lack a tyrosine kinase mutation or over-express EGFR is unlikely to result in clinical response. Published by Elsevier Inc.