Kazanov Diana, Shapira Itzhak, Pick Marjorie, Kolker Olga, Liberman Eliezer, Deutsch Varda, Strier Loudmilla, Dvory-Sobol Hadas, Kunik Talya, Arber Nadir
Gastrointestinal Oncology Unit, Tel Aviv Medical Center and Tel Aviv University, Tel Aviv, Israel.
Dig Dis Sci. 2003 Jul;48(7):1251-61. doi: 10.1023/a:1024138605802.
Cyclin D1 plays an important role in the multi-step process of gastrointestinal tumorigenesis. We hypothesize that normal enterocytes over-expressing cyclin D1 will demonstrate a transformed phenotype. The nontumorigenic intestinal epithelial cell line, IEC-18, was transfected with the vector pMV7-CCND1, encoding cyclin D1. Three clones, with cyclin D1 levels similar to those seen in colon cancer cell lines, were further evaluated in comparison to the vector control cells. They proliferated faster and demonstrated anchorage-independent growth in soft agar, higher saturation density, and higher plating efficiency. When injected into nude mice, tumors were generated after 6-8 weeks. On the other hand these cells were more sensitive to induction of apoptosis. There was no change in the level of beta-catenin protein. In conclusion, cyclin D1 can act as an oncogene in vitro and in vivo, when produced in immortalized normal intestinal epithelial cells. This model may be useful for understanding the role and interrelationships of cyclin D1 in colorectal tumorigenesis.
细胞周期蛋白D1在胃肠道肿瘤发生的多步骤过程中起重要作用。我们假设过表达细胞周期蛋白D1的正常肠上皮细胞将表现出转化表型。用编码细胞周期蛋白D1的载体pMV7-CCND1转染非致瘤性肠上皮细胞系IEC-18。与载体对照细胞相比，进一步评估了三个细胞周期蛋白D1水平与结肠癌细胞系相似的克隆。它们增殖更快，在软琼脂中表现出不依赖贴壁的生长、更高的饱和密度和更高的接种效率。当注射到裸鼠体内时，6-8周后会产生肿瘤。另一方面，这些细胞对凋亡诱导更敏感。β-连环蛋白的蛋白水平没有变化。总之，当在永生化的正常肠上皮细胞中产生时，细胞周期蛋白D1在体外和体内都可作为癌基因。该模型可能有助于理解细胞周期蛋白D1在结直肠癌发生中的作用及相互关系。
