Sarti Manuela, Sevignani Cinzia, Calin George A, Aqeilan Rami, Shimizu Masayoshi, Pentimalli Francesca, Picchio Maria Cristina, Godwin Andrew, Rosenberg Anne, Drusco Alessandra, Negrini Massimo, Croce Carlo M
Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA, USA.
Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):806-13.
The human TESTIN (TES) gene is a putative tumor suppressor gene in the fragile chromosomal region FRA7G at 7q31.1/2 that was reported to be altered in leukemia and lymphoma cell lines. In this report, we investigated the effect of TES gene expression in vivo to evaluate a possible role of TES gene in human cancer.
We have analyzed the expression of TES gene in a panel of 25 breast tumors and 17 cell lines of breast, colon, and uterine cancers. Furthermore, to evaluate the potential of TES gene therapy, we studied the effects of adenoviral TES transduction (Ad-TES) in cell lines with undetectable TES expression (T47D and MES-SA) as well as in MCF-7 cell line where TES expression is normal.
Twenty-five percent of primary breast tumor samples as well as the breast cancer cell line T47D and the uterine sarcoma cell line MES-SA were negative or displayed low levels of TES. After TES restoration by Ad-TES transduction, T47D and MES-SA cell lines underwent apoptosis. Furthermore, TES expression significantly reduced the tumorigenic potential of both T47D and MES-SA in nude mice, whereas the untreated cells and Ad-GFP-infected cells showed tumor growth in vivo. The TES-positive cell line control (MCF-7) was not affected by TES expression and did not show a reduction of tumorigenicity in nude mice after infection with Ad-TES.
Ad-TES expression inhibit the growth of breast and uterine cancer cells lacking of TES expression through caspase-dependent and caspase-independent apoptosis, respectively, suggesting that Ad-TES infection should be explored as a therapeutic strategy.
人类TESTIN（TES）基因是位于7q31.1/2的脆性染色体区域FRA7G中的一个假定肿瘤抑制基因，据报道在白血病和淋巴瘤细胞系中发生改变。在本报告中，我们研究了TES基因在体内表达的影响，以评估TES基因在人类癌症中的可能作用。
我们分析了25个乳腺肿瘤以及17个乳腺癌、结肠癌和子宫癌细胞系中TES基因的表达。此外，为了评估TES基因治疗的潜力，我们研究了腺病毒介导的TES转导（Ad-TES）对TES表达检测不到的细胞系（T47D和MES-SA）以及TES表达正常的MCF-7细胞系的影响。
25%的原发性乳腺肿瘤样本以及乳腺癌细胞系T47D和子宫肉瘤细胞系MES-SA为TES阴性或低表达。通过Ad-TES转导恢复TES表达后，T47D和MES-SA细胞系发生凋亡。此外，TES表达显著降低了T47D和MES-SA在裸鼠中的致瘤潜力，而未处理的细胞和Ad-GFP感染的细胞在体内显示出肿瘤生长。TES阳性细胞系对照（MCF-7）不受TES表达的影响，在感染Ad-TES后裸鼠中的致瘤性也未降低。
Ad-TES表达分别通过半胱天冬酶依赖性和非依赖性凋亡抑制缺乏TES表达的乳腺癌和子宫癌细胞的生长，提示应探索Ad-TES感染作为一种治疗策略。
