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Pax-6 在促进乳腺癌细胞增殖和肿瘤发生中的可能作用。

Possible role of Pax-6 in promoting breast cancer cell proliferation and tumorigenesis.

机构信息

Department of Breast Surgery, Zhejiang Provincial Cancer Hospital, Hangzhou 310022, China.

出版信息

BMB Rep. 2011 Sep;44(9):595-600. doi: 10.5483/bmbrep.2011.44.9.595.

DOI:10.5483/bmbrep.2011.44.9.595
PMID:21944253
Abstract

Pax 6, a member of the paired box (Pax) family, has been implicated in oncogenesis. However, its therapeutic potential has been never examined in breast cancer. To explore the role of Pax6 in breast cancer development, a lentivirus based short hairpin RNA (shRNA) delivery system was used to knockdown Pax6 expression in estrogen receptor (ER)-positive (MCF-7) and ER-negative (MDA-MB-231) breast cancer cells. Effect of Pax6 silencing on breast cancer cell proliferation and tumorigenesis was analyzed. Pax6-RNAi-lentivirus infection remarkably downregulated the expression levels of Pax6 mRNA and protein in MCF-7 and MDA-MB-231 cells. Accordingly, the cell viability, DNA synthesis, and colony formation were strongly suppressed, and the tumorigenesis in xenograft nude mice was significantly inhibited. Moreover, tumor cells were arrested at G0/G1 phase after Pax6 was knocked down. Pax6 facilitates important regulatory roles in breast cancer cell proliferation and tumor progression, and could serve as a diagnostic marker for clinical investigation.

摘要

配对盒基因 6(Pax 6)是配对盒(Pax)家族的成员之一,其与肿瘤的发生有关。然而,Pax 6 在乳腺癌中的治疗潜力尚未得到研究。为了探索 Pax 6 在乳腺癌发生发展中的作用,本研究采用基于慢病毒的短发夹 RNA(shRNA)传递系统敲低了雌激素受体(ER)阳性(MCF-7)和 ER 阴性(MDA-MB-231)乳腺癌细胞中的 Pax6 表达。分析了 Pax6 沉默对乳腺癌细胞增殖和致瘤性的影响。Pax6-RNAi-慢病毒感染可显著下调 MCF-7 和 MDA-MB-231 细胞中 Pax6 mRNA 和蛋白的表达水平。相应地,细胞活力、DNA 合成和集落形成受到强烈抑制,异种移植裸鼠的肿瘤发生也受到显著抑制。此外,敲低 Pax6 后,肿瘤细胞被阻滞在 G0/G1 期。Pax 6 在乳腺癌细胞增殖和肿瘤进展中发挥重要的调节作用,可作为临床研究的诊断标志物。

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