Constitutive expression of Rb associated protein 46 (RbAp46) reverts transformed phenotypes of breast cancer cells.
Constitutive expression of Rb associated protein 46 (RbAp46) reverts transformed phenotypes of breast cancer cells.
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发表时间：
2003-09
影响因子：
2
通讯作者：
Teng-fei Zhang;Shui-Qing Yu;T. Deuel;Zhaoyi Wang
中科院分区：
文献类型：
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作者：
Teng-fei Zhang;Shui-Qing Yu;T. Deuel;Zhaoyi Wang
视网膜母细胞瘤（Rb）抑制相关蛋白46（RbAp 46）是染色质修饰和重塑复合物的亚基。此前，我们发现RbAp 46作为一种有效的生长抑制剂发挥作用。它也是Wilms肿瘤抑制因子WT 1的下游效应子。WT 1的表达水平在乳腺癌细胞系和原发性乳腺肿瘤亚群中下调的发现使我们研究RbAp 46在乳腺癌肿瘤发生中的可能作用。在这里，我们发现，RbAp 46的表达水平下降，在五个建立的乳腺癌细胞系相比，正常的乳腺上皮细胞系。为了研究RbAp 46组成型表达对乳腺癌细胞转化表型的影响，我们使用三种乳腺癌细胞系MCF-7、MDA-MB-231和MDA-MB-436建立了组成型表达外源性RbAp 46的稳定细胞系。我们发现RbAp 46表达抑制了这些乳腺癌细胞在软琼脂中的集落形成，并抑制了这些细胞在裸鼠中的肿瘤形成。我们的数据表明，组成型RbAp 46表达抑制乳腺癌细胞的转化表型，并建议RbAp 46表达失调可能有助于乳腺癌肿瘤的发生。
The retinoblastoma (Rb) suppressor associated protein 46 (RbAp46) is a subunit of chromatin modifying and remodeling complexes. Previously, we found that RbAp46 functions as a potent growth inhibitor. It is also a downstream effector of the Wilms' tumor suppressor, WT1. The findings that expression levels of WT1 were down-regulated in breast cancer cell lines and in subsets of primary breast tumors led us to investigate the possible role of RbAp46 in breast cancer tumorigenesis. Here, we found that RbAp46 expression levels were decreased in five established breast cancer cell lines compared to a normal mammary gland epithelial cell line. To investigate the effect of constitutive expression of RbAp46 on the transformed phenotypes of breast cancer cells, we established stable cell lines that constitutively express exogenous RbAp46 using three breast cancer cell lines, MCF-7, MDA-MB-231 and MDA-MB-436. We have found that RbAp46 expression suppressed colony formation of these breast cancer cells in soft-agar, and inhibited tumor formation of these cells in nude mice. Our data demonstrated that constitutive RbAp46 expression suppresses the transformed phenotypes of breast cancer cells, and suggested that dysregulation of RbAp46 expression may contribute to breast cancer tumorigenesis.