CTIP2 expression in human head and neck squamous cell carcinoma is linked to poorly differentiated tumor status.
CTIP2 expression in human head and neck squamous cell carcinoma is linked to poorly differentiated tumor status.
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DOI：
10.1371/journal.pone.0005367
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Indra AK
中科院分区：
文献类型：
--
作者：
Ganguli-Indra G;Wasylyk C;Liang X;Millon R;Leid M;Wasylyk B;Abecassis J;Indra AK
我们先前已经证明CTIP 2在胚胎发育和成年期在小鼠皮肤中高度表达。CTIP 2突变小鼠在出生时死亡，具有表皮分化缺陷和受损的表皮通透性屏障，表明其在皮肤发育和/或稳态中的作用。CTIP 2也被认为在细胞中起肿瘤抑制剂的作用，并且一些报道已经描述了CTIP 2的染色体重排和人T细胞急性淋巴母细胞白血病（T-ALL）之间的联系。本研究的目的是探讨CTIP 2在头颈部鳞状细胞癌（HNSCC）中的表达模式。在本研究中，我们分析了CTIP 2的表达在人HNSCC细胞系的蛋白质印迹法，石蜡包埋的档案标本的免疫组织化学（IHC），并在cDNA样本的人HNSCC的qRT-PCR。在几种HNSCC细胞系中检测到CTIP 2蛋白水平升高。CTIP 2主要表达于头颈部正常上皮的基底层。发现CTIP 2表达在HNSCC中显著升高（p<0.01），并且CTIP 2表达的增加与低分化肿瘤状态相关。CTIP 2蛋白和癌症干细胞（CSC）标记物BMI 1的核共定位在中等分化和低分化肿瘤中表达BMI 1的大多数（如果不是全部）细胞中观察到。我们首次报道了转录调节因子CTIP 2在正常人头颈部上皮细胞中的表达。在人头颈部肿瘤的低分化样品中检测到CTIP 2表达的统计学显著增加。发现实际CTIP 2而不是CTIP 2的长形式（CTIP 2L）与肿瘤的分化状态更相关。结果表明存在表达CTIP 2的不同癌细胞亚群，并强调使用CTIP 2和BMI 1共标记来区分肿瘤起始细胞或癌症干细胞（CSC）与周围癌细胞。
We have demonstrated earlier that CTIP2 is highly expressed in mouse skin during embryogenesis and in adulthood. CTIP2 mutant mice die at birth with epidermal differentiation defects and a compromised epidermal permeability barrier suggesting its role in skin development and/or homeostasis. CTIP2 has also been suggested to function as tumor suppressor in cells, and several reports have described a link between chromosomal rearrangements of CTIP2 and human T cell acute lymphoblast leukemia (T-ALL). The aim of the present study was to look into the pattern of CTIP2 expression in Head and Neck Squamous Cell Carcinoma (HNSCC). In the present study, we analyzed CTIP2 expression in human HNSCC cell lines by western blotting, in paraffin embedded archival specimens by immunohistochemistry (IHC), and in cDNA samples of human HNSCC by qRT-PCR. Elevated levels of CTIP2 protein was detected in several HNSCC cell lines. CTIP2 staining was mainly detected in the basal layer of the head and neck normal epithelium. CTIP2 expression was found to be significantly elevated in HNSCC (p<0.01), and increase in CTIP2 expression was associated with poorly differentiated tumor status. Nuclear co-localization of CTIP2 protein and cancer stem cell (CSC) marker BMI1 was observed in most, if not all of the cells expressing BMI1 in moderately and poorly differentiated tumors. We report for the first time expression of transcriptional regulator CTIP2 in normal human head and neck epithelia. A statistically significant increase in the expression of CTIP2 was detected in the poorly differentiated samples of the human head and neck tumors. Actual CTIP2, rather than the long form of CTIP2 (CTIP2L) was found to be more relevant to the differentiation state of the tumors. Results demonstrated existence of distinct subsets of cancer cells, which express CTIP2 and underscores the use of CTIP2 and BMI1 co-labeling to distinguish tumor initiating cells or cancer stem cells (CSCs) from surrounding cancer cells.
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影响因子：
1.2
作者：
Leid, M;Ishmael, JE;Dollé, P
通讯作者：
Dollé, P
影响因子：
3.7
作者：
Mack, Brigitte;Gires, Olivier
通讯作者：
Gires, Olivier
影响因子：
11.2
作者：
Godlewski, Jakub;Nowicki, Michal O.;Lawler, Sean
通讯作者：
Lawler, Sean
影响因子：
4.1
作者：
Avram, D;Fields, A;Leid, M
通讯作者：
Leid, M
影响因子：
11.2
作者：
Chiba, Tetsuhiro;Miyagi, Satoru;Iwama, Atsushi
通讯作者：
Iwama, Atsushi