Velcich A, Corner G, Palumbo L, Augenlicht L
Department of Oncology, Albert Einstein Cancer Center/Montefiore Medical Center, Bronx, New York 10467, USA.
Oncogene. 1999 Apr 22;18(16):2599-606. doi: 10.1038/sj.onc.1202610.
On 18q, frequently deleted in late stage colorectal cancers, a gene, Deleted in Colon Cancer (DCC), has been identified and postulated to play a role as a tumor suppressor gene. DCC is retained in the majority of mucinous tumors, which produce high levels of mucins, and seems to be preferentially expressed in intestinal goblet cells. To investigate whether DCC is related to mucin expression and can modulate the transformed phenotype, we introduced a full-length DCC cDNA into HT29 cells, which can be induced in vitro to express MUC2, the gene that encodes the major colonic mucin. Expression of DCC did not modulate constitutive or induced expression of MUC2, nor did DCC induce a mature goblet cell phenotype. However, HT29 clones expressing high and low levels of DCC protein showed a significant decrease in cell proliferation and tumorigenicity. Furthermore, increased shedding and an elevated rate of spontaneous apoptosis were associated with higher levels of expression of DCC. In summary, while restoration of DCC expression in a human colon carcinoma cell line did not influence expression of differentiation markers, DCC expression did affect the growth and tumorigenic properties of the cells suggesting that DCC can modulate the malignant phenotype of colon cancer.
在18号染色体长臂上，该区域在晚期结直肠癌中经常缺失，一个名为结肠癌缺失基因（DCC）的基因已被鉴定出来，并被推测作为一种肿瘤抑制基因发挥作用。DCC在大多数产生高水平粘蛋白的粘液性肿瘤中保留，并且似乎在肠道杯状细胞中优先表达。为了研究DCC是否与粘蛋白表达相关并能调节转化表型，我们将全长DCC cDNA导入HT29细胞，该细胞在体外可被诱导表达MUC2，即编码主要结肠粘蛋白的基因。DCC的表达并未调节MUC2的组成型或诱导型表达，DCC也未诱导成熟杯状细胞表型。然而，表达高水平和低水平DCC蛋白的HT29克隆在细胞增殖和致瘤性方面显著降低。此外，DCC表达水平升高与脱落增加和自发凋亡率升高相关。总之，虽然在人结肠癌细胞系中恢复DCC表达不影响分化标志物的表达，但DCC表达确实影响细胞的生长和致瘤特性，表明DCC可调节结肠癌的恶性表型。
