Chung D C, Brown S B, Graeme-Cook F, Seto M, Warshaw A L, Jensen R T, Arnold A
Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
J Clin Endocrinol Metab. 2000 Nov;85(11):4373-8. doi: 10.1210/jcem.85.11.6937.
The molecular pathogenesis of human pancreatic endocrine tumors (PETs) is poorly understood. Three independent animal models have pointed to the pivotal role of the G1/S cell cycle transition in pancreatic endocrine cell proliferation. We thus hypothesized that the cell cycle regulator cyclin D1 may contribute to the pathogenesis of human PETs. Overexpression of cyclin D1 was identified in 43% of cases, and no correlation was observed with clinical phenotype. The novel observation of frequent overexpression of cyclin D1 suggests that this established oncogene may be implicated in the pathogenesis of human PETs. The absence of detectable alterations in cyclin D1 genomic structure suggests that the mechanism for its oncogenic activation in PETs may be transcriptional or posttranscriptional.
人类胰腺内分泌肿瘤（PETs）的分子发病机制尚不清楚。三种独立的动物模型表明G1/S细胞周期转换在胰腺内分泌细胞增殖中起关键作用。因此，我们推测细胞周期调节因子细胞周期蛋白D1可能在人类PETs的发病机制中起作用。在43%的病例中发现了细胞周期蛋白D1的过表达，且未观察到与临床表型的相关性。细胞周期蛋白D1频繁过表达这一新发现表明，这种已确定的癌基因可能与人类PETs的发病机制有关。细胞周期蛋白D1基因组结构未检测到改变，这表明其在PETs中致癌激活的机制可能是转录或转录后水平的。
