HP1β is a biomarker for breast cancer prognosis and PARP inhibitor therapy.
HP1β is a biomarker for breast cancer prognosis and PARP inhibitor therapy.
复制标题
DOI：
10.1371/journal.pone.0121207
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Ann DK
中科院分区：
文献类型：
--
作者：
Lee YH;Liu X;Qiu F;O'Connor TR;Yen Y;Ann DK
异染色质蛋白1家族成员（HP 1 α、β和γ）主要与异染色质相关，在基因调控和DNA损伤反应中发挥重要作用。单个HP 1亚型的表达改变对细胞增殖和肿瘤发生具有深远影响。我们分析了HP 1家族的表达谱的数据挖掘，使用已发表的微阵列数据集结合回顾性免疫组织化学分析存档的乳腺癌生物标本。我们发现过表达HP 1 β mRNA的患者组与低分化乳腺肿瘤和显著较低的生存率相关。针对HP 1 α、HP 1 β和HP 1 γ的免疫组织化学染色显示，在乳腺癌中，各自的HP 1表达水平经常改变。57.4- 60.1%的检查样本显示高HP 1 β表达，39.9 - 42.6%的检查肿瘤显示每种HP 1亚型无表达或低表达。有趣的是，对HP 1表达谱和乳腺癌标志物的比较分析揭示了所有三种HP 1亚型的各自表达水平与Ki-67（细胞增殖和众所周知的乳腺癌标志物）之间的正相关性。为了探索单个HP 1对PARP抑制剂治疗乳腺癌的作用，用PARP抑制剂ABT-888与或不与卡铂一起处理MCF 7乳腺癌细胞和单独HP 1耗尽的MCF 7细胞。值得注意的是，HP 1 β敲低细胞对单独的PARP抑制剂ABT-888及其与卡铂的组合超敏。总之，虽然HP 1 β表达增加与乳腺癌的不良预后相关，但HP 1 β丰度受损可作为化疗（包括PARP抑制剂）治疗乳腺癌的有用预测标志物。
Members of the heterochromatin protein 1 family (HP1α, β and γ) are mostly associated with heterochromatin and play important roles in gene regulation and DNA damage response. Altered expression of individual HP1 subtype has profound impacts on cell proliferation and tumorigenesis. We analyzed the expression profile of HP1 family by data mining using a published microarray data set coupled with retrospective immunohistochemistry analyses of archived breast cancer biospecimens. We found that the patient group overexpressing HP1β mRNA is associated with poorly differentiated breast tumors and with a significantly lower survival rate. Immunohistochemical staining against HP1α, HP1β and HP1γ shows that respective HP1 expression level is frequently altered in breast cancers. 57.4 - 60.1% of samples examined showed high HP1β expression and 39.9 - 42.6 % of examined tumors showed no or low expression of each HP1 subtype. Interestingly, comparative analysis on HP1 expression profile and breast cancer markers revealed a positive correlation between the respective expression level of all three HP1 subtypes and Ki-67, a cell proliferation and well-known breast cancer marker. To explore the effect of individual HP1 on PARP inhibitor therapy for breast cancer, MCF7 breast cancer cells and individually HP1-depleted MCF7 cells were treated with PARP inhibitor ABT-888 with or without carboplatin. Notably, HP1β-knockdown cells are hypersensitive to the PARP inhibitor ABT-888 alone and its combination with carboplatin. In summary, while increased HP1β expression is associated with the poor prognosis in breast cancer, compromised HP1β abundance may serve as a useful predictive marker for chemotherapy, including PARP inhibitors against breast cancer.
登录
查看更多内容
通过使用BRCA1和BRCA2同源模型的ABT-888（PARP抑制剂）和卡铂的组合增强合成致死性。
影响因子：
5.7
作者：
Clark CC;Weitzel JN;O'Connor TR
通讯作者：
O'Connor TR
DOI：
10.1083/jcb.200904033
发表时间：
2009-05-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ball AR Jr;Yokomori K
通讯作者：
Yokomori K
影响因子：
11.2
作者：
McCabe, Nuala;Turner, Nicholas C.;Ashworth, Alan
通讯作者：
Ashworth, Alan
影响因子：
4.3
作者：
Dedes, Konstantin J.;Wilkerson, Paul M.;Reis-Filho, Jorge S.
通讯作者：
Reis-Filho, Jorge S.
影响因子：
50.3
作者：
Neve, Richard M.;Chin, Koei;Gray, Joe W.
通讯作者：
Gray, Joe W.