Department of Biochemistry and Molecular Biology, Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA.
J Cell Physiol. 2010 Nov;225(3):875-87. doi: 10.1002/jcp.22298.
Core binding factor (CBF) is a transcription factor complex that plays roles in development, stem-cell homeostasis, and human disease. CBF is a heterodimer composed of one of three DNA-binding RUNX proteins plus the non-DNA-binding protein, CBFβ. Recent studies have showed that the RUNX factors exhibit complex expression patterns in prostate, breast, and ovarian cancers, and CBF has been implicated in the control of cancer-related genes. However, the biologic roles of CBF in solid tumors have not been fully elucidated. To test whether CBF is required for the malignant phenotype of various epithelial cancers, we used lentiviral delivery of CBFβ-specific shRNA to significantly decrease CBFβ expression in two prostate cancer cell lines (PPC1 and PC-3) and the SKOV-3 ovarian cancer cell line. We found that knockdown of CBFβ significantly inhibited anchorage independent growth of each cell line. Further, CBFβ knockdown in PPC1 cells suppressed xenograft tumor growth compared to controls. Mice injected with SKOV-3 ovarian cancer cells knocked-down for CBFβ exhibited a survival time similar to control mice. However, human cells recovered from the ascites fluid of these mice showed CBFβ expression levels similar to those from mice injected with control SKOV-3 cells, suggesting that CBFβ knockdown is incompatible with tumor cell growth. Gene expression profiling of CBFβ knockdown cells revealed significant changes in expression in genes involved in various developmental and cell signaling pathways. These data collectively suggest that CBFβ is required for malignancy in some human cancers.
核心结合因子（CBF）是一种转录因子复合物，在发育、干细胞稳态和人类疾病中发挥作用。CBF 是由三种 DNA 结合 RUNX 蛋白之一与非 DNA 结合蛋白 CBFβ组成的异二聚体。最近的研究表明，RUNX 因子在前列腺癌、乳腺癌和卵巢癌中表现出复杂的表达模式，CBF 已被牵连到控制与癌症相关的基因。然而，CBF 在实体瘤中的生物学作用尚未完全阐明。为了测试 CBF 是否是各种上皮癌恶性表型所必需的，我们使用慢病毒递送 CBFβ 特异性 shRNA 显著降低了两种前列腺癌细胞系（PPC1 和 PC-3）和 SKOV-3 卵巢癌细胞系中的 CBFβ 表达。我们发现，CBFβ 的敲低显著抑制了每个细胞系的锚定非依赖性生长。此外，与对照相比，PPC1 细胞中 CBFβ 的敲低抑制了异种移植肿瘤的生长。与对照小鼠相比，注射了 CBFβ 敲低的 SKOV-3 卵巢癌细胞的小鼠的存活时间相似。然而，从这些小鼠的腹水回收的人细胞显示出与注射对照 SKOV-3 细胞的小鼠相似的 CBFβ 表达水平，表明 CBFβ 的敲低与肿瘤细胞的生长不相容。CBFβ 敲低细胞的基因表达谱分析显示，参与各种发育和细胞信号通路的基因表达发生了显著变化。这些数据共同表明，CBFβ 是一些人类癌症恶性肿瘤所必需的。
