Tumorigenesis and Neoplastic Progression Brk Protects Breast Cancer Cells from Autophagic Cell Death Induced by Loss of Anchorage
Tumorigenesis and Neoplastic Progression Brk Protects Breast Cancer Cells from Autophagic Cell Death Induced by Loss of Anchorage
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肿瘤发生和肿瘤进展 Brk 保护乳腺癌细胞免受因锚定丧失引起的自噬性细胞死亡
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通讯作者：
T. Torigoe
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作者：
S. Hashimoto;Y. Tabuchi;Hideaki Yurino;Y. Hirohashi;S. Deshimaru;T. Asano;Tasuku Mariya;K. Oshima;Y. Takamura;Y. Ukita;A. Ametani;N. Kondo;Norikazu Monma;T. Takeda;Sadahiko Misu;Toshitugu Okayama;K. Ikeo;Tsuyoshi Saito;S. Kaneko;Yutaka Suzuki;M. Hattori;K. Matsushima;T. Torigoe
Brk是一种酪氨酸激酶，在大多数乳腺肿瘤中表达，但在正常乳腺组织中不表达，促进乳腺癌细胞增殖。正常上皮细胞依赖于细胞-细胞或细胞-基质相互作用存活，并在这些相互作用破坏后发生凋亡。肿瘤细胞对细胞凋亡的诱导不太敏感，并且被预测具有扩散的潜力。我们通过将Brk的表达与肿瘤分级相关联并证明其在非粘附条件下调节癌细胞存活的作用，研究了Brk在乳腺肿瘤进展中是否具有进一步的作用。通过逆转录PCR对从人乳腺癌手术样品中提取的RNA测定Brk表达。当Brk蛋白水平被RNA干扰抑制时，检查悬浮培养中的乳腺癌细胞存活。另外，评估了在Brk阴性乳腺癌细胞中实验性过表达Brk的效果。Brk mRNA表达在3级乳腺肿瘤中明显高于较低肿瘤级别。在悬浮培养中，Brk抑制增加细胞死亡率，与对照组相比，这种细胞死亡程序表现出自噬的特征，但不是凋亡。相反，Brk阴性细胞中Brk的实验表达
Brk, a tyrosine kinase expressed in a majority of breast tumors, but not normal mammary tissue, promotes breast carcinoma cell proliferation. Normal epithelial cells are dependent on cell–cell or cell–matrix interactions for survival and undergo apoptosis after disruption of these interactions. Tumor cells are less sensitive to the induction of apoptosis and are predicted to have the potential to disseminate. We inves-tigated whether Brk has further roles in breast tumor progression by relating its expression to tumor grade and demonstrating its role in the regulation of carcinoma cell survival under non-adherent conditions. Brk expression was determined by reverse transcription PCR on RNA extracted from surgical samples of human breast cancers. Breast carcinoma cell survival in suspension culture was examined when Brk protein levels were suppressed by RNA interference. Addition-ally, the effect of experimentally overexpressing Brk in otherwise Brk-negative breast carcinoma cells was assessed. Brk mRNA expression was notably higher in grade 3 breast tumors, as compared with lower tumor grades. In suspension culture, Brk suppression increased the rate of cell death, as compared with controls, and this cell death program exhibited characteristics of autophagy but not of apoptosis. Conversely, experimental expression of Brk in Brk-negative cells