Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer
Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer
复制标题
DOI：
10.1158/0008-5472.can-04-0416
复制
发表时间：
2004-09-01
期刊：
影响因子：
11.2
通讯作者：
Katano, M
中科院分区：
文献类型：
--
作者：
Kubo, M;Nakamura, M;Katano, M
Hedgehog(HH)信号通路在胚胎发育中起着组织者的作用。遗传分析表明，HH途径在乳腺形态发生中起着关键作用。HH途径的一个组成部分Patched1的中断会导致乳腺导管的异常生长。最近的研究表明，在不同类型的恶性肿瘤中，HH途径被结构性激活。然而，目前还不清楚这一途径是否在人类乳腺癌中被激活。在这里，我们通过免疫组织化学染色检测了52例人乳腺癌组织中HH通路的成分，包括Sonic HH、Patched1和Gli1的表达。与癌旁正常组织相比，52例肿瘤组织均呈高强度Gli1染色。Gli1的核染色率与雌激素受体的表达及组织学类型有关。环多巴胺是一种类固醇生物碱，可以阻断HH途径，暴露在这种环境中会抑制Gli1的表达，并抑制HH途径激活的乳腺癌细胞的生长。这些数据表明，HH通路是乳腺癌治疗靶点的新候选基因。
The Hedgehog (Hh) signaling pathway functions as an organizer in embryonic development. Genetic analysis has demonstrated a critical role for the Hh pathway in mammary gland morphogenesis. Disruption of Patched1, a component of the Hh pathway, results in abnormal growth of mammary duct. Recent studies have shown constitutive activation of the Hh pathway in various types of malignancies. However, it remains unclear whether this pathway is activated in human breast cancer. Here, we determined the expression of the components, including Sonic Hh, Patched1, and Gli1, of the Hh pathway by immunohistochemical staining in a series of 52 human breast carcinomas. All of 52 tumors display staining of high intensity for Gli1 when compared with adjacent normal tissue. The nuclear staining ratio of Gli1 correlates with expression of estrogen receptor and histologic type. Exposure to cyclopamine, a steroidal alkaloid that blocks the Hh pathway, suppresses expression of Gli1 and the growth of the Hh pathway-activated breast carcinoma cells. These data indicate that the Hh pathway is a new candidate for therapeutic target of breast cancer.