Tomkova K, El-Rifai W, Vilgelm A, Kelly M C, Wang T C, Zaika A I
Department of Surgery, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Oncogene. 2006 Sep 28;25(44):6032-6. doi: 10.1038/sj.onc.1209610. Epub 2006 Apr 24.
p73, a new p53 family member, is a transcription factor that is increasingly recognized in cancer research as an important player in tumorigenesis as well as in chemotherapeutic drug sensitivity. Despite the substantial structural and functional similarities to p53, accumulating evidence suggests that p53 and p73 may differently regulate their transcriptional targets. In this study, we have investigated the role of p73 in regulation of the gastrin gene promoter. Gastrin is a peptide hormone and an important factor in determining the progression of a number of human malignancies. Our results show that p73 can bind to the gastrin promoter. This leads to transcriptional upregulation of gastrin mRNA. We also found that the levels of gastrin and p73 transcripts correlate in primary gastric tumors. Taken together, our results demonstrate a novel mechanism for regulation of gastrin gene transcription and support a concept that p53 and p73 may have different biological roles in tumors.
p73是一种新的p53家族成员,作为一种转录因子,它在癌症研究中越来越被认为是肿瘤发生以及化疗药物敏感性方面的重要参与者。尽管p73与p53在结构和功能上有很大的相似性,但越来越多的证据表明,p53和p73可能以不同的方式调节它们的转录靶点。在本研究中,我们研究了p73在胃泌素基因启动子调控中的作用。胃泌素是一种肽类激素,是决定多种人类恶性肿瘤进展的重要因素。我们的结果表明,p73可以结合胃泌素启动子。这导致胃泌素mRNA的转录上调。我们还发现,在原发性胃肿瘤中,胃泌素和p73转录本的水平相关。综上所述,我们的结果证明了胃泌素基因转录调控的一种新机制,并支持p53和p73在肿瘤中可能具有不同生物学作用的概念。