Department of Medical Oncology, Cancer Center, The State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041, China.
Biomed Res Int. 2013;2013:976765. doi: 10.1155/2013/976765. Epub 2013 Jun 22.
The RAS-association domain family 1 A (RASSF1A) is a classical member of RAS effectors regulating cell proliferation and apoptosis. Loss of RASSF1A expression may shift the balance towards a growth-promoting effect without the necessity of activating K-ras mutations. Its potential association with K-ras mutations in colorectal cancer (CRC) is unclear.
RASSF1A expression was examined in normal mucosa, adenoma, and tumor tissues of colon and rectum, respectively. We examined the association of RASSF1A expression, mutations of K-ras, and EGFR status in 76 primary CRCs. The relationship between clinicopathological characteristics and RASSF1A expression was also analyzed.
RASSF1A expression level decreased progressively in normal mucosa, adenoma and, tumor tissues, and the loss of RASSF1A expression occurred more frequently in tumor tissues. Of 76 primary CRCs, loss of RASSF1A expression and/or K-ras mutations were detected in 77% cases. Loss of RASSF1A expression was more frequent in K-ras wild-type than in mutation cases (63% versus 32%, P = 0.011).
Our study indicates that loss of RASSF1A may be involved in pathogenesis of CRC, its expression was found predominantly in K-ras wild-type CRCs, suggesting that it may be another way of affecting RAS signaling, in addition to K-ras mutations.
RAS 相关结构域家族 1A（RASSF1A）是调节细胞增殖和凋亡的 RAS 效应物的经典成员。RASSF1A 表达缺失可能会使细胞生长促进作用的平衡发生倾斜，而无需激活 K-ras 突变。其与结直肠癌（CRC）中 K-ras 突变的潜在关联尚不清楚。
分别检测了结肠和直肠的正常黏膜、腺瘤和肿瘤组织中的 RASSF1A 表达。我们检测了 76 例原发性 CRC 中 RASSF1A 表达、K-ras 突变和 EGFR 状态的相关性。还分析了 RASSF1A 表达与临床病理特征之间的关系。
RASSF1A 表达水平在正常黏膜、腺瘤和肿瘤组织中逐渐降低，且肿瘤组织中 RASSF1A 表达缺失更为频繁。在 76 例原发性 CRC 中，77%的病例存在 RASSF1A 表达缺失和/或 K-ras 突变。RASSF1A 表达缺失在 K-ras 野生型病例中比突变病例更为常见（63%比 32%，P = 0.011）。
我们的研究表明，RASSF1A 的缺失可能参与了 CRC 的发病机制，其表达主要存在于 K-ras 野生型 CRC 中，表明其可能是除 K-ras 突变之外影响 RAS 信号通路的另一种方式。
