The Hedgehog Signaling Pathway Plays an Essential Role in Maintaining the CD 44 + CD 24 – / low Subpopulation and the Side Population of Breast Cancer Cells

The Hedgehog Signaling Pathway Plays an Essential Role in Maintaining the CD 44 + CD 24 – / low Subpopulation and the Side Population of Breast Cancer Cells
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发表时间:
2009
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通讯作者:
Haruo Tanaka;Masafumi Nakamura;C. Kameda;M. Kubo;N. Sato;S. Kuroki;Masao Tanaka;M. Katano
Haruo Tanaka;Masafumi Nakamura;C. Kameda;M. Kubo;N. Sato;S. Kuroki;Masao Tanaka;M. Katano
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其他
文献类型:
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作者:
Haruo Tanaka;Masafumi Nakamura;C. Kameda;M. Kubo;N. Sato;S. Kuroki;Masao Tanaka;M. Katano

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在不同的研究中报道了侧群(SP)和CD44+/CD24 - /低群比其他群包含更多的致瘤细胞,并且具有形成新肿瘤和在乳腺癌组织中进行异质性分化的能力。然而,这两种人群之间的关系尚未在乳腺癌细胞中得到探讨。结果表明,SP和CD44+/CD24 - /low基因群是重叠的。两个种群对紫杉醇均有耐药性。与其他群体相比,这些细胞群体中Hedgehog (Hh)信号通路的mRNA和蛋白水平的表达更高。此外,Hh信号活性的抑制抑制了两个种群的增殖。Hh信号通路的反激活因子Gli1对两个种群的增殖的影响证实了Hh信号活性在这两个种群的增殖中的重要性。这些数据表明Hh信号通路对乳腺癌致瘤细胞群的增殖至关重要,并且该通路可能代表乳腺癌治疗靶向的新候选
The side population (SP) and the CD44+/CD24–/low population have been reported in separate studies to include more tumorigenic cells than other populations, and to have the ability to form new tumors and undergo heterogeneous differentiation in breast cancer tissue. However, the relationship between these two populations has not yet been explored in breast cancer cells. Here it is shown that the SP and the CD44+/CD24–/low populations are overlapping. Both populations were resistant to paclitaxel. Components of the Hedgehog (Hh) signaling pathway were more highly expressed in these cell populations at both the mRNA and protein levels compared with other populations. Furthermore, inhibition of Hh signaling activity suppressed the proliferation of both populations. The significance of Hh signaling activity in the proliferation of both populations was confirmed by the effect of an si-RNA against Gli1, a transactivator of the Hh signaling pathway, on the proliferation of both populations. These data suggest that the Hh signaling pathway is essential for the proliferation of the tumorigenic population of breast cancer cells, and that this pathway might represent a new candidate for breast cancer therapy targeting