Tumor suppressor function of Syk in human MCF10A in vitro and normal mouse mammary epithelium in vivo.
Tumor suppressor function of Syk in human MCF10A in vitro and normal mouse mammary epithelium in vivo.
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DOI：
10.1371/journal.pone.0007445
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发表时间：
2009-10-15
期刊：
影响因子：
3.7
通讯作者：
Mueller SC
中科院分区：
文献类型：
--
作者：
Sung YM;Xu X;Sun J;Mueller D;Sentissi K;Johnson P;Urbach E;Seillier-Moiseiwitsch F;Johnson MD;Mueller SC
Syk在发育或成年乳腺上皮中的正常功能尚不清楚，然而，Syk抑制乳腺癌细胞中的肿瘤生长、侵袭和转移。在这里，我们证明，在小鼠乳腺，一个Syk等位基因的损失大大增加增殖和导管分支和入侵的上皮细胞通过乳腺脂肪垫在青春期。乳腺癌发展一年。Syk还抑制体外增殖和侵袭。MCF 10A乳腺上皮细胞中Syk的siRNA或shRNA敲低显著增加增殖、锚定非依赖性生长、细胞运动性和侵袭，形成功能性的细胞外基质降解侵袭伪足。Syk敲除后的形态学和基因微阵列分析显示，管腔和分化上皮特征的丧失，上皮向间质转化，以及侵袭足细胞表面标志物CD44、CD49F和MMP 14的增加。这些结果支持Syk在正常形态发生过程中限制上皮细胞增殖和侵袭的作用，并强调Syk作为乳腺癌肿瘤抑制因子的关键作用。系统性抗Syk治疗后乳腺癌风险的问题被提出，因为只有部分损失的Syk足以诱导乳腺癌。
The normal function of Syk in epithelium of the developing or adult breast is not known, however, Syk suppresses tumor growth, invasion, and metastasis in breast cancer cells. Here, we demonstrate that in the mouse mammary gland, loss of one Syk allele profoundly increases proliferation and ductal branching and invasion of epithelial cells through the mammary fat pad during puberty. Mammary carcinomas develop by one year. Syk also suppresses proliferation and invasion in vitro. siRNA or shRNA knockdown of Syk in MCF10A breast epithelial cells dramatically increased proliferation, anchorage independent growth, cellular motility, and invasion, with formation of functional, extracellular matrix-degrading invadopodia. Morphological and gene microarray analysis following Syk knockdown revealed a loss of luminal and differentiated epithelial features with epithelial to mesenchymal transition and a gain in invadopodial cell surface markers CD44, CD49F, and MMP14. These results support the role of Syk in limiting proliferation and invasion of epithelial cells during normal morphogenesis, and emphasize the critical role of Syk as a tumor suppressor for breast cancer. The question of breast cancer risk following systemic anti-Syk therapy is raised since only partial loss of Syk was sufficient to induce mammary carcinomas.
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DOI：
10.1186/bcr1673
发表时间：
2007
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Fillmore C;Kuperwasser C
通讯作者：
Kuperwasser C
影响因子：
4.8
作者：
Debnath, J;Muthuswamy, SK;Brugge, JS
通讯作者：
Brugge, JS
影响因子：
2.7
作者：
Kokkinos, Maria I.;Wafai, Razan;Waltham, Mark
通讯作者：
Waltham, Mark
影响因子：
2
作者：
Bebu, Ionut;Mathew, Thomas
通讯作者：
Mathew, Thomas
影响因子：
8
作者：
Bindels, S.;Mestdagt, M.;Gilles, C.
通讯作者：
Gilles, C.