The Tip60 lysine acetyltransferase is a tumor suppressor in most cancers but an oncogene in prostate and gastric cancer. Tip60 is commonly found in the nucleus, where it acetylates proteins involved in transcription, DNA repair, and chromatin; however, it has also been shown to acetylate cytoplasmic targets. In this study, we investigated the relationship between Tip60 localization and breast and lung cancer. In cell fractionation experiments, cancer-derived cell lines showed a shift from nuclear to cytoplasmic endogenous Tip60 compared with cell lines derived from normal cells. With immunofluorescence, we observed four different localization patterns of overexpressed Tip60 and found that cancer cells had increased cytoplasmic localization of Tip60 compared with HEK-293 cells. The addition of a nuclear localization signal (NLS) increased the number of cells containing nuclear Tip60, whereas mutation of a putative endogenous NLS increased the number of cells with cytoplasmic Tip60. Overexpression of Tip60 increased cancer cell line sensitivity to paclitaxel regardless of changes in localization. These results suggest that dysregulation of Tip60 in breast and lung cancer is not limited to reduced expression but may also involve subcellular localization.

中文翻译：

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Tip60抑癌活性在乳腺癌和肺癌细胞中不需要核定位。

Tip60赖氨酸乙酰基转移酶在大多数癌症中均是肿瘤抑制因子，但在前列腺癌和胃癌中是癌基因。Tip60通常在细胞核中发现，在那里乙酰化与转录，DNA修复和染色质有关的蛋白质。然而，它也被证明可以乙酰化细胞质靶标。在这项研究中，我们调查了Tip60定位与乳腺癌和肺癌之间的关系。在细胞分离实验中，与正常细胞来源的细胞系相比，癌症来源的细胞系显示出从核内向内源性Tip60的转变。通过免疫荧光，我们观察到过表达的Tip60的四种不同的定位模式，并且发现与HEK-293细胞相比，癌细胞的Tip60的细胞质定位增加了。加入核定位信号（NLS）会增加含有核Tip60的细胞数量，而推定的内源性NLS的突变会增加具有胞质Tip60的细胞数量。Tip60的过表达增加了癌细胞系对紫杉醇的敏感性，无论定位如何变化。这些结果表明，乳腺癌和肺癌中Tip60的失调不仅限于表达降低，还可能涉及亚细胞定位。