Hedgehog signaling pathway mediates the progression of non-invasive breast cancer to invasive breast cancer
Hedgehog signaling pathway mediates the progression of non-invasive breast cancer to invasive breast cancer
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DOI：
10.1111/j.1349-7006.2010.01779.x
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发表时间：
2011-02-01
期刊：
影响因子：
5.7
通讯作者：
Katano, Mitsuo
中科院分区：
文献类型：
--
作者：
Souzaki, Masae;Kubo, Makoto;Katano, Mitsuo
本研究的目的是阐明Hedgehog信号通路（Hh pathway）在导管原位癌（DCIS）向浸润性导管癌（IDC）发展中的作用。共149例手术切除的乳腺疾病标本和12个前哨淋巴结微转移（Ly-met）进行了研究。Hh通路活化的程度由癌细胞中的Gli1核染色比率（%Gli1核易位）估计。乳腺癌细胞的侵袭性使用Matrigel测定来确定。证实了非肿瘤性疾病中Gli1核转位至IDC的百分比连续增加。在肿瘤标本中，%Gli1核转位与每种类型乳腺疾病的侵袭性相关，也与侵袭相关的组织病理学参数相关。淋巴结微转移组Gli1核转位率与原发灶组相似，高于DCIS伴微浸润组和DCIS组。阻断Hh通路可降低乳腺癌细胞的侵袭力。在IDC中，%Gli1核转位与雌激素受体-a的表达相关。雌激素可增加Gli1核转位率和雌激素受体a阳性细胞的侵袭力。Hh通路介导从非侵袭性表型向侵袭性表型的进展，并且%Gli1核转位可用作评估侵袭性能力的预测标志物。（Cancer Sci 2011; 102：373 - 381）
The purpose of this study is to clarify the contribution of the Hedgehog signaling pathway (Hh pathway) to the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). A total of 149 surgically resected mammary disease specimens and 12 sentinel lymph nodes with micro-metastasis (Ly-met) were studied. The degree of Hh pathway activation was estimated from the Gli1 nuclear staining ratio (%Gli1 nuclear translocation) in cancer cells. The invasiveness of breast cancer cells was determined using Matrigel assays. A serial increase of %Gli1 nuclear translocation to IDC from non-neoplastic diseases was confirmed. In tumor specimens, %Gli1 nuclear translocation correlated with the invasiveness of each type of mammary disease and also correlated with invasion-related histopathological parameters. The %Gli1 nuclear translocation in lymph nodes with micro-metastasis was similar to that in primary sites and higher than that in DCIS with microinvasion and DCIS. Blockade of the Hh pathway decreased the invasiveness of breast cancer cells. In IDC, %Gli1 nuclear translocation correlated with the expression of estrogen receptor-a. Estrogen increased %Gli1 nuclear translocation and the invasiveness of estrogen receptor-a-positive cells. The Hh pathway mediates progression from a non-invasive phenotype to an invasive phenotype and %Gli1 nuclear translocation may be useful as a predictive marker for evaluating the ability of invasiveness. (Cancer Sci 2011; 102: 373-381)