Radiation acts on the microenvironment to affect breast carcinogenesis by distinct mechanisms that decrease cancer latency and affect tumor type.
Radiation acts on the microenvironment to affect breast carcinogenesis by distinct mechanisms that decrease cancer latency and affect tumor type.
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DOI：
10.1016/j.ccr.2011.03.011
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发表时间：
2011-05-17
期刊：
影响因子：
50.3
通讯作者：
Barcellos-Hoff MH
中科院分区：
文献类型：
--
作者：
Nguyen DH;Oketch-Rabah HA;Illa-Bochaca I;Geyer FC;Reis-Filho JS;Mao JH;Ravani SA;Zavadil J;Borowsky AD;Jerry DJ;Dunphy KA;Seo JH;Haslam S;Medina D;Barcellos-Hoff MH
组织微环境是肿瘤发生的重要决定因素。我们证明，电离辐射，一种已知的致癌物质，影响癌症的频率和特点，通过作用于微环境。使用乳腺嵌合体模型，其中照射的主机与致癌Trp 53空上皮移植，我们显示了加速发展的侵袭性肿瘤的分子特征是不同的非照射主机。分子和遗传学方法表明TGFβ介导肿瘤加速;分子特征涉及TGFβ，遗传性降低TGFβ消除了对潜伏期的影响。令人惊讶的是，来自辐射宿主的肿瘤主要是雌激素受体阴性的。这种作用不依赖于TGFβ，与乳腺干细胞活性有关。因此，照射的微环境通过不同的和意想不到的机制影响癌症的潜伏期和临床相关特征。
Tissue microenvironment is an important determinant of carcinogenesis. We demonstrate that ionizing radiation, a known carcinogen, affects cancer frequency and characteristics by acting on the microenvironment. Using a mammary chimera model in which an irradiated host is transplanted with oncogenic Trp53 null epithelium, we show accelerated development of aggressive tumors whose molecular signatures were distinct from non-irradiated hosts. Molecular and genetic approaches show that TGFβ mediated tumor acceleration; molecular signatures implicated TGFβ and genetically reducing TGFβ abrogated the effect on latency. Surprisingly, tumors from irradiated hosts were predominantly estrogen receptor negative. This effect was TGFβ independent and linked to mammary stem cell activity. Thus the irradiated microenvironment affects latency and clinically relevant features of cancer through distinct and unexpected mechanisms.
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DOI：
10.1016/j.ijrobp.2009.09.004
发表时间：
2010-02-01
影响因子：
7
作者：
Broeks, Annegien;Braaf, Linde M.;Van't Veer, Laura J.
通讯作者：
Van't Veer, Laura J.
影响因子：
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作者：
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影响因子：
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作者：
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Tagliabue, Elda
影响因子：
45.3
作者：
Harvey, JM;Clark, GM;Allred, DC
通讯作者：
Allred, DC
影响因子：
11.5
作者：
Allred, D. Craig;Wu, Yun;Medina, Dan
通讯作者：
Medina, Dan