Division of Gynecologic Oncology, Oregon Health & Science University, Portland, OR 97239, USA.
Transl Oncol. 2009 Dec;2(4):341-9. doi: 10.1593/tlo.09199.
We tested the hypothesis that co-coordinated up-regulation or down-regulation of several ovarian cell surface kinases may provide clues for better understanding of the disease and help in rational design of therapeutic targets.
We compared the expression signature of 69 surface kinases in normal ovarian surface epithelial cells (OSE), with OSE from patients at high risk and with ovarian cancer.
Seven surface kinases, ALK, EPHA5, EPHB1, ERBB4, INSRR, PTK, and TGFbetaR1 displayed a distinctive linear trend in expression from normal, highrisk, and malignant epithelium. We confirmed these results using semiquantitative reverse transcription-polymerase chain reaction and tissue array of 202 ovarian cancer samples. A strong correlate was shown between disease-free survival and the expression of ERBB4. DNA sequencing revealed two novel mutations in ERBB4 in two cancer samples.
A distinct subset of the ovarian surface kinome is altered in the transition from high risk to invasive cancer and genetic mutation is not a dominant mechanism for these modifications. These results have significant implications for early detection and targeted therapeutic approaches for women at high risk of developing ovarian cancer.
我们检验了这样一个假设，即多个卵巢细胞表面激酶的协调上调或下调可能为更好地理解该疾病提供线索，并有助于合理设计治疗靶点。
我们比较了 69 种表面激酶在正常卵巢表面上皮细胞（OSE）、高危 OSE 和卵巢癌中的表达特征。
七种表面激酶（ALK、EPHA5、EPHB1、ERBB4、INSRR、PTK 和 TGFbetaR1）的表达从正常、高危和恶性上皮呈明显的线性趋势。我们使用半定量逆转录-聚合酶链反应和 202 个卵巢癌样本的组织阵列验证了这些结果。ERBB4 的表达与无病生存呈强相关性。DNA 测序显示在两个癌症样本中 ERBB4 有两个新的突变。
从高危到浸润性癌的转变过程中，卵巢表面激酶组的一个明显子集发生了改变，基因突变不是这些改变的主要机制。这些结果对高危女性的早期检测和靶向治疗方法具有重要意义。
