Aberrant APOBEC3B Expression in Breast Cancer Is Linked to Proliferation and Cell Cycle Phase.
Aberrant APOBEC3B Expression in Breast Cancer Is Linked to Proliferation and Cell Cycle Phase.
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DOI：
10.3390/cells12081185
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发表时间：
2023-04-18
期刊：
影响因子：
6
通讯作者：
Span, Paul N. N.
中科院分区：
文献类型：
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作者：
Roelofs, Pieter A. A.;Timmermans, Mieke A. M.;Stefanovska, Bojana;den Boestert, Myrthe A. A.;van den Borne, Amber W. M.;Balcioglu, Hayri E. E.;Trapman, Anita M. M.;Harris, Reuben S. S.;Martens, John W. M.;Span, Paul N. N.
APOBEC 3B（A3 B）在一部分乳腺癌中异常过表达，与晚期疾病、预后不良和治疗耐药性有关，但乳腺癌中A3 B失调的原因仍不清楚。在此，使用RT-qPCR和多重免疫荧光成像定量不同细胞系和乳腺肿瘤中的A3 B mRNA和蛋白表达水平，并将其与细胞周期标志物相关。在细胞周期期间诱导A3 B表达在细胞周期同步化后用多种方法另外解决。首先，我们发现细胞系和肿瘤内的A3 B蛋白水平是异质性的，并且与细胞周期的G2/M期的特征性增殖标记物Cyclin B1强烈相关。其次，在多个乳腺癌细胞系中，观察到高A3 B的表达水平在整个细胞周期中振荡，并再次与细胞周期蛋白B1相关。第三，A3 B表达的诱导在整个G 0/早期G1期被有效抑制，可能是通过RB/E2 F途径效应蛋白。第四，在低A3 B的细胞中，通过PKC/ncNF-κB途径诱导A3 B主要发生在活跃增殖的细胞中，并且在G 0期停滞的细胞中基本上不存在。总而言之，这些结果支持一个模型，其中乳腺癌中失调的A3 B过表达是细胞周期的G2/M期期间增殖相关的抑制缓解与伴随的通路激活的累积结果。
APOBEC3B (A3B) is aberrantly overexpressed in a subset of breast cancers, where it associates with advanced disease, poor prognosis, and treatment resistance, yet the causes of A3B dysregulation in breast cancer remain unclear. Here, A3B mRNA and protein expression levels were quantified in different cell lines and breast tumors and related to cell cycle markers using RT-qPCR and multiplex immunofluorescence imaging. The inducibility of A3B expression during the cell cycle was additionally addressed after cell cycle synchronization with multiple methods. First, we found that A3B protein levels within cell lines and tumors are heterogeneous and associate strongly with the proliferation marker Cyclin B1 characteristic of the G2/M phase of the cell cycle. Second, in multiple breast cancer cell lines with high A3B, expression levels were observed to oscillate throughout the cell cycle and again associate with Cyclin B1. Third, induction of A3B expression is potently repressed throughout G0/early G1, likely by RB/E2F pathway effector proteins. Fourth, in cells with low A3B, induction of A3B through the PKC/ncNF-κB pathway occurs predominantly in actively proliferating cells and is largely absent in cells arrested in G0. Altogether, these results support a model in which dysregulated A3B overexpression in breast cancer is the cumulative result of proliferation-associated relief from repression with concomitant pathway activation during the G2/M phase of the cell cycle.
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影响因子：
30.8
作者：
Burns, Michael B.;Temiz, Nuri A.;Harris, Reuben S.
通讯作者：
Harris, Reuben S.
影响因子：
13.6
作者：
Law EK;Sieuwerts AM;LaPara K;Leonard B;Starrett GJ;Molan AM;Temiz NA;Vogel RI;Meijer-van Gelder ME;Sweep FC;Span PN;Foekens JA;Martens JW;Yee D;Harris RS
通讯作者：
Harris RS
影响因子：
5.5
作者：
Gazova, Iveta;Lefevre, Lucas;Summers, Kim M.
通讯作者：
Summers, Kim M.
影响因子：
12.3
作者：
Kanu N;Cerone MA;Goh G;Zalmas LP;Bartkova J;Dietzen M;McGranahan N;Rogers R;Law EK;Gromova I;Kschischo M;Walton MI;Rossanese OW;Bartek J;Harris RS;Venkatesan S;Swanton C
通讯作者：
Swanton C
影响因子：
6.4
作者：
通讯作者：
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