Loss of FHIT expression in cervical carcinoma cell lines and primary tumors.
Loss of FHIT expression in cervical carcinoma cell lines and primary tumors.
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发表时间：
1997-11
期刊：
影响因子：
11.2
通讯作者：
D. Greenspan;D. Connolly;R. Wu;R. Y. Lei;Joshua T C Vogeistein;Young-Tak Kim;J. Mok;Nubia Mufloz;F. Bosch;K. Shah;Kathleen R. Cho;Spain
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作者：
D. Greenspan;D. Connolly;R. Wu;R. Y. Lei;Joshua T C Vogeistein;Young-Tak Kim;J. Mok;Nubia Mufloz;F. Bosch;K. Shah;Kathleen R. Cho;Spain
在宫颈癌中经常观察到涉及 3 号染色体短臂 (3p13-21.1) 的等位基因缺失。最近，候选抑癌基因 FHIT（脆弱组氨酸三联体）被克隆并定位到该染色体区域 (3p14.2)。先前已在多种肿瘤细胞系和原发性癌中鉴定出异常的 FHIT 转录本，尽管它们的重要性及其起源的分子机制仍未完全确定。此外，在宫颈癌 FHIT 基因座内的脆弱位点 (FRA3B) 上发现了人乳头瘤病毒 DNA 的整合。这些观察结果促使我们评估宫颈癌细胞系、原发性宫颈癌和正常组织中的 FHIT mRNA 和蛋白表达。预期大小和序列的转录物是在培养的角质形成细胞和所有评估的正常组织中通过逆转录 (RT)-PCR 鉴定的主要种类。相比之下，异常的 FHIT 转录本在 7 个宫颈癌细胞系中的 6 个和 25 个原发性宫颈癌中的 17 个（68%）中很容易得到证实。 Northern 印迹分析表明，宫颈癌细胞系中 FHIT 表达减少或缺失，尤其是 RT-PCR 产物异常的细胞系。对宫颈组织中 Fhit 表达的免疫组织化学分析显示，非肿瘤性鳞状和腺状宫颈上皮具有很强的免疫反应性，并且 33 例原发性宫颈癌中的 25 例 (76%) 中 Fhit 蛋白显着减少或丢失。在那些通过 RT-PCR 检测发现 FHIT 转录物完全异常或缺失的宫颈癌细胞系和原发性肿瘤中，Fhit 蛋白表达总是显着降低或缺失。 FHIT 表达在许多宫颈癌中频繁发生变化，但在正常组织中却没有，这表明 FHIT 基因改变可能在宫颈肿瘤发生中发挥重要作用。
Allelic deletions involving the short arm of chromosome 3 (3p13-21.1) have been observed frequently in cervical carcinomas. Recently, a candidate tumor suppressor gene, FHIT (Fragile Histidine Triad), was cloned and mapped to this chromosomal region (3p14.2). Abnormal FHIT transcripts have been identified previously in a variety of tumor cell lines and primary carcinomas, although their significance and the molecular mechanisms underlying their origin remain incompletely defined. In addition, integration of human papillomavirus DNA has been identified at a fragile site (FRA3B) within the FHIT locus in cervical cancer. These observations motivated us to evaluate FHIT mRNA and protein expression in cervical cancer cell lines, primary cervical carcinomas, and normal tissues. Transcripts of the expected size and sequence were the predominant species identified by reverse transcription (RT)-PCR in cultured keratinocytes and all normal tissues evaluated. In contrast, aberrant FHIT transcripts were readily demonstrated in 6 of 7 cervical carcinoma cell lines and 17 of 25 (68%) primary cervical carcinomas. Northern blot analyses demonstrated reduced or absent FHIT expression in the cervical carcinoma cell lines, particularly those with aberrant RT-PCR products. Immunohistochemical analysis of Fhit expression in cervical tissues revealed strong immunoreactivity in nonneoplastic squamous and glandular cervical epithelium and marked reduction or loss of Fhit protein in 25 of 33 (76%) primary cervical carcinomas. In those cervical cancer cell lines and primary tumors with exclusively aberrant or absent FHIT transcripts by RT-PCR, Fhit protein expression was always markedly reduced or absent. The frequent alterations in FHIT expression in many cervical carcinomas, but not in normal tissues, suggest that FHIT gene alterations may play an important role in cervical tumorigenesis.