Establishment and characterization of a cell line from smokeless tobacco associated oral squamous cell carcinoma
Establishment and characterization of a cell line from smokeless tobacco associated oral squamous cell carcinoma
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DOI：
10.1016/s1368-8375(03)00084-8
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发表时间：
2003-12-01
期刊：
影响因子：
4.8
通讯作者：
Ralhan, R
中科院分区：
文献类型：
--
作者：
Kaur, J;Ralhan, R
一个细胞系，AMOS-III已建立从手术切除标本的未经治疗的原发性人类口腔鳞状细胞癌的口底从慢性无烟烟草消费者。免疫细胞化学分析显示AMOS-III细胞中的上皮特异性抗原、细胞角蛋白5、10、13和16以及整合素α（6）标志物，证实了细胞系的上皮谱系。细胞形态学、超微结构、核型、贴壁生长和免疫细胞化学分析表明，细胞系具有上皮转化表型。细胞AMOS-III细胞的怀疑时间为42-44 h。染色体的Giemsa带型证实了AMOS-III细胞的人类起源。对癌症相关基因产物p53和p21（cip 1）/（waf 1）的分子分析显示存在野生型p21（cip 1）/（waf 1）和截短的p53蛋白。维甲酸在预防口腔癌患者第二原发肿瘤发生中的作用的分子机制仍有待明确。用10（-4）μ M的全反式视黄酸（ATRA）处理AMOS-III细胞导致81%的细胞死亡。ATRA处理后p21（cip 1）/（waf 1）表达增强，维甲酸受体核转位和凋亡细胞死亡。因此，该细胞系为阐明无烟烟草诱导的口腔癌中涉及p53失活和p21（cip 1）/（waf 1）过表达的机制提供了体外模型。此外，该细胞系的ATRA反应性强调了其在识别口腔癌细胞中类维生素A反应分子靶点方面的潜在用途。(C)2003 Elsevier Ltd.保留所有权利。
A cell tine, AMOS-III has been established from the surgically resected specimen of an untreated primary human oral squamous cell carcinoma of the floor of mouth from a chronic smokeless tobacco consumer. Immunocytochemical analysis showed epithelial specific antigen, cytokeratins 5, 10, 13 and 16 and integrin alpha(6) markers in AMOS-III cells, confirming the epithelial lineage of the cell line. Analyses of morphology, ultrastructure, karyotype, anchorage independent growth and immunocytochemical properties of the cell tine demonstrated the transformed phenotype of epithelial. cells. AMOS-III cells have doubting time of 42-44 h. Giemsa-banding patterns of chromosomes confirmed the human origin of the AMOS-III cells. Molecular analysis of cancer-related gene products, p53 and p21(cip1)/(waf1) showed the presence of wild type p21(cip1)/(waf1) and truncated p53 proteins. The molecular mechanism underlying the action of retinoids in preventing the occurrence of second primary tumors in oral cancer patients remain to be clearly defined. Treatment of AMOS-III cells with all-trans retinoic acid (ATRA) at 10(-4) muM resulted in 81% cell death. ATRA treatment resulted in enhanced expression of p21(cip1)/(waf1), nuclear transtocation of retinoic acid receptors and apoptotic cell death. Thus, this cell tine provides an in vitro model for elucidating the mechanism involving p53 inactivation and p21(cip1)/(waf1) overexpression in smokeless tobacco-induced oral cancer. Furthermore, the ATRA responsiveness of the cell line underscores its potential utility in identifying the retinoid responsive molecular targets in oral cancer cells. (C) 2003 Elsevier Ltd. All rights reserved.