Pagotto U, Arzberger T, Theodoropoulou M, Grübler Y, Pantaloni C, Saeger W, Losa M, Journot L, Stalla G K, Spengler D
Max Planck Institute of Psychiatry, Munich, Germany.
Cancer Res. 2000 Dec 15;60(24):6794-9.
The ZAC gene encodes a new zinc-finger protein that concomitantly induces apoptosis and cell cycle arrest and localizes to chromosome 6q24-q25, a well-known hot spot related to cancer. ZAC is highly expressed in the anterior pituitary gland, and its ablation by antisense targeting promotes pituitary cell proliferation. Here we investigate ZAC status in pituitary tumors to evaluate its role in pituitary tumorigenesis. Interest ingly, a strong reduction or absence of ZAC mRNA and protein expres sion was detected in nonfunctioning pituitary adenomas, whereas in clin ically active pituitary neoplasias, the decrease in ZAC expression was variable. Loss of expression was not associated with a mutation of the ZAC gene. Our observations suggest that alternative mechanisms of gene inactivation and/or altered regulation of the ZAC gene occur in nonfunctioning pituitary adenomas.
ZAC基因编码一种新的锌指蛋白，该蛋白可同时诱导细胞凋亡和细胞周期停滞，并定位于6号染色体q24 - q25区域，这是一个与癌症相关的著名热点区域。ZAC在前脑垂体中高度表达，通过反义靶向作用使其缺失可促进垂体细胞增殖。在此，我们研究垂体肿瘤中的ZAC状态，以评估其在垂体肿瘤发生中的作用。有趣的是，在无功能垂体腺瘤中检测到ZAC mRNA和蛋白表达显著降低或缺失，而在临床有活性的垂体肿瘤中，ZAC表达的降低则有所不同。表达缺失与ZAC基因的突变无关。我们的观察结果表明，在无功能垂体腺瘤中存在基因失活的替代机制和/或ZAC基因调控的改变。
