Radiation-induced reprogramming of breast cancer cells.
Radiation-induced reprogramming of breast cancer cells.
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DOI：
10.1002/stem.1058
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发表时间：
2012-05
期刊：
影响因子：
5.2
通讯作者：
Pajonk, Frank
中科院分区：
文献类型：
--
作者：
Lagadec, Chann;Vlashi, Erina;Della Donna, Lorenza;Dekmezian, Carmen;Pajonk, Frank
乳腺癌被认为是分层组织的，少数乳腺癌干细胞（BCSC）能够重新生长肿瘤，而它们的后代缺乏这种能力。最近，几个研究组报道了当乳腺癌经受经典抗癌治疗时BCSC的富集。然而，导致这种富集的潜在机制尚未完全了解。使用从患者样本中分选的非BCSC，我们发现电离辐射将分化的乳腺癌细胞重编程为诱导的BCSC（iBCSC）。iBCSC表现出增加的乳腺球形成，增加的致瘤性，并表达与来自非辐照样品的BCSC相同的干细胞相关基因。重编程发生在细胞的多倍体亚群中，与转录因子Oct 4、Sox-2、Nanog和Klf 4的重新表达相一致，并且可以通过Notch抑制而部分阻止。我们的结论是，辐射可能会诱导分化的乳腺癌细胞的BCSC表型，这种机制有助于增加BCSC的数量后看到经典的抗癌治疗。
Breast cancers are thought to be organized hierarchically with a small number of breast cancer stem cells (BCSCs) able to re-grow a tumor while their progeny lack this ability. Recently, several groups reported enrichment for BCSCs when breast cancers were subjected to classical anticancer treatment. However, the underlying mechanisms leading to this enrichment are incompletely understood. Using non-BCSCs sorted from patient samples, we found that ionizing radiation reprogrammed differentiated breast cancer cells into induced BCSCs (iBCSCs). iBCSCs showed increased mammosphere formation, increased tumorigenicity and expressed the same stemness-related genes as BCSCs from non-irradiated samples. Reprogramming occurred in a polyploid subpopulation of cells, coincided with re-expression of the transcription factors Oct4, Sox-2, Nanog, and Klf4, and could be partially prevented by Notch inhibition. We conclude that radiation may induce a BCSC phenotype in differentiated breast cancer cells and that this mechanism contributes to increased BCSC numbers seen after classical anti-cancer treatment.
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DOI：
10.1186/bcr920
发表时间：
2004
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Dontu G;Jackson KW;McNicholas E;Kawamura MJ;Abdallah WM;Wicha MS
通讯作者：
Wicha MS
影响因子：
7.4
作者：
Fillmore, Christine M.;Kuperwasser, Charlotte
通讯作者：
Kuperwasser, Charlotte
DOI：
10.4161/cc.8.20.9701
发表时间：
2009-10-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Heddleston JM;Li Z;McLendon RE;Hjelmeland AB;Rich JN
通讯作者：
Rich JN
DOI：
10.1186/bcr3019
发表时间：
2011-09-27
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Beltran AS;Rivenbark AG;Richardson BT;Yuan X;Quian H;Hunt JP;Zimmerman E;Graves LM;Blancafort P
通讯作者：
Blancafort P
影响因子：
3.5
作者：
Bese, NS;Sut, PA;Ober, A
通讯作者：
Ober, A