哥伦比亚大学构建出清除肿瘤细胞的转录因子基因

研究前列腺癌啮齿动物模型的癌症研究人员，使用腺病毒载体移植了两种转录因子，PEA-3和AP-1，这两种转录因子选择性激活肿瘤抑制基因清除癌细胞，但是不会损伤正常组织。

哥伦比亚大学医学中心的研究人员构建了一种包含转录因子PEA-3和AP-1的腺病毒载体。目前已知这些因子能够触发无活性PROM-PEG癌蛋白转化为一种凋亡起始子，活性PEG-3(progression-elevated gene-3)。PROM-PEG通常在癌细胞中大量存在，但是在正常细胞中并不存在。

研究结果发表在2005年1月25日的《美国国家科学院进展》上，解释了接受了该载体的小鼠肿瘤死亡而正常组织没有受到影响。PEA-1/AP-1结合也对黑色素瘤、卵巢、乳房和神经胶质瘤（大脑）等肿瘤同样有作用。

哥伦比亚大学医学中心临床病理教授、主要作者Paul B.Fisher医生 说：“令人高兴的是我们现在能够设计出仅仅针对并清除癌细胞的治疗方法。我们希望这种方法能够特别清除我们不能看见的转移性肿瘤，这种肿瘤不能被手术或者放疗清除。基因治疗，特别对癌症，正在开始治疗的新纪元。”
 
Transcription Factor Genes Kill Tumors
 
Cancer researchers working with a rodent model for prostate cancer have used an adenovirus vector to implant the genes for two transcription factors, PEA-3 and AP-1, which selectively activated a tumor-suppressing gene and eradicated the cancer cells without harming normal tissues.

Investigators at Columbia University Medical Center (New York, NY, USA) created an adenovirus vector containing the genes for the transcription factors PEA-3 and AP-1. These factors were known to trigger the conversion of inactive PROM-PEG cancer protein into active PEG-3 (progression-elevated gene-3), an apoptosis initiator. PROM-PEG is generally found in abundance in cancer cells but is not present in normal cells.

Results published in the January 25, 2005, issue of the Proceedings of the [U.S.] National Academy of Sciences revealed that tumors in mice receiving the vector died while normal tissues were not affected. The PEA-1/AP-1 combination was also found to act on melanoma, ovarian, breast, and glioma (brain) tumors.

“What is exciting is we may now be able to design a therapy that will seek out and destroy only cancer cells,” said senior author, Dr. Paul B. Fisher, professor of clinical pathology at Columbia University Medical Center. “We hope it will be particularly powerful in eradicating metastases that we cannot see and that cannot be eliminated by surgery or radiation. Gene therapy, especially for cancer, is really starting to make a comeback.”