Pallante Pierlorenzo, Federico Antonella, Berlingieri Maria Teresa, Bianco Mimma, Ferraro Angelo, Forzati Floriana, Iaccarino Antonino, Russo Maria, Pierantoni Giovanna Maria, Leone Vincenza, Sacchetti Silvana, Troncone Giancarlo, Santoro Massimo, Fusco Alfredo
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli Federico II, Naples, Italy .
Cancer Res. 2008 Aug 15;68(16):6770-8. doi: 10.1158/0008-5472.CAN-08-0695.
Using gene expression profiling, we found that the CBX7 gene was drastically down-regulated in six thyroid carcinoma cell lines versus control cells. The aims of this study were to determine whether CBX7 is related to the thyroid cancer phenotype and to try to identify new tools for the diagnosis and prognosis of thyroid cancer. We thus evaluated CBX7 expression in various snap-frozen and paraffin-embedded thyroid carcinoma tissues of different degrees of malignancy by quantitative reverse transcription-PCR and immunohistochemistry, respectively. CBX7 expression progressively decreased with malignancy grade and neoplasia stage. Indeed, it decreased in an increasing percentage of cases going from benign adenomas to papillary (PTC), follicular, and anaplastic (ATC) thyroid carcinomas. This finding coincides with results obtained in rat and mouse models of thyroid carcinogenesis. CBX7 loss of heterozygosity occurred in 36.8% of PTC and in 68.7% of ATC. Restoration of CBX7 expression in thyroid cancer cells reduced growth rate, with a retention in the G(1) phase of the cell cycle, suggesting that CBX7 can contribute to the proliferation of the transformed thyroid cells. In conclusion, loss of CBX7 expression correlates with a highly malignant phenotype in thyroid cancer patients.
通过基因表达谱分析,我们发现与对照细胞相比,CBX7基因在六种甲状腺癌细胞系中显著下调。本研究的目的是确定CBX7是否与甲状腺癌表型相关,并试图找到用于甲状腺癌诊断和预后的新工具。因此,我们分别通过定量逆转录PCR和免疫组织化学方法评估了不同恶性程度的各种速冻和石蜡包埋的甲状腺癌组织中CBX7的表达。CBX7的表达随着恶性程度分级和肿瘤分期而逐渐降低。事实上,从良性腺瘤到乳头状(PTC)、滤泡状和未分化(ATC)甲状腺癌,其表达降低的病例百分比逐渐增加。这一发现与甲状腺癌发生的大鼠和小鼠模型中获得的结果一致。36.8%的PTC和68.7%的ATC发生了CBX7杂合性缺失。甲状腺癌细胞中CBX7表达的恢复降低了生长速率,细胞周期停滞在G(1)期,这表明CBX7可能促进转化的甲状腺细胞增殖。总之,CBX7表达缺失与甲状腺癌患者的高恶性表型相关。