Genetic predisposition directs breast cancer phenotype by dictating progenitor cell fate.
Genetic predisposition directs breast cancer phenotype by dictating progenitor cell fate.
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DOI：
10.1016/j.stem.2010.12.007
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发表时间：
2011-02-04
期刊：
影响因子：
23.9
通讯作者：
Kuperwasser C
中科院分区：
文献类型：
--
作者：
Proia TA;Keller PJ;Gupta PB;Klebba I;Jones AD;Sedic M;Gilmore H;Tung N;Naber SP;Schnitt S;Lander ES;Kuperwasser C
BRCA1基因遗传突变的女性患乳腺癌的风险增加，但也表现出发展侵袭性基底样乳腺肿瘤的倾向。我们在这里报告，乳腺上皮细胞来源于患者窝藏有害突变BRCA1（BRCA1mut/+）引起肿瘤的基础分化增加相对于细胞BRCA1 +/+患者。对BRCA1mut/+患者的无病乳腺组织的分子分析显示，即使在癌症发生之前，祖细胞谱系定型也存在缺陷。此外，我们发现转录抑制因子Slug是人乳腺祖细胞谱系定型和分化的重要功能调节因子，并且在BRCA1mut/+组织中异常表达。在肿瘤转化之前和之后，Slug表达对于增加的基底样表型是必要的。这些发现表明，患者群体的遗传背景，除了影响发病率，显着影响祖细胞命运的承诺，因此，肿瘤表型。
Women with inherited mutations in the BRCA1 gene have increased risk of developing breast cancer, but also exhibit a predisposition for the development of aggressive basal-like breast tumors. We report here that breast epithelial cells derived from patients harboring deleterious mutations in BRCA1 (BRCA1mut/+) give rise to tumors with increased basal differentiation relative to cells from BRCA1+/+ patients. Molecular analysis of disease-free breast tissues from BRCA1mut/+ patients revealed defects in progenitor cell lineage commitment even before cancer incidence. Moreover, we discovered that the transcriptional repressor Slug is an important functional regulator of human breast progenitor cell lineage commitment and differentiation and that it is aberrantly expressed in BRCA1mut/+ tissues. Slug expression is necessary for increased basal-like phenotypes prior to and following neoplastic transformation. These findings demonstrate that the genetic background of patient populations, in addition to affecting incidence rates, significantly impacts progenitor cell fate commitment and, therefore, tumor phenotype.
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影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
影响因子：
11.2
作者：
Burga LN;Tung NM;Troyan SL;Bostina M;Konstantinopoulos PA;Fountzilas H;Spentzos D;Miron A;Yassin YA;Lee BT;Wulf GM
通讯作者：
Wulf GM
DOI：
10.1073/pnas.0401064101
发表时间：
2004-04-06
影响因子：
11.1
作者：
Kuperwasser, C;Chavarria, T;Weinberg, RA
通讯作者：
Weinberg, RA
DOI：
10.1073/pnas.0503793102
发表时间：
2005-06-28
影响因子：
11.1
作者：
Furuta, S;Jiang, XZ;Lee, WH
通讯作者：
Lee, WH
影响因子：
11.5
作者：
Arnes, JB;Brunet, JS;Foulkes, WD
通讯作者：
Foulkes, WD