Toh Y, Oki E, Oda S, Tokunaga E, Ohno S, Maehara Y, Nicolson G L, Sugimachi K
Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Int J Cancer. 1997 Aug 22;74(4):459-63. doi: 10.1002/(sici)1097-0215(19970822)74:4<459::aid-ijc18>3.0.co;2-4.
The mta1 gene is a recently identified novel candidate metastasis-associated gene. The deduced amino acid sequence contains an src homology-3 domain binding motif, a zinc finger motif and possible phosphorylation sites, suggesting that this gene is involved in signal transduction or regulation of gene expression. The purpose of our study was to examine the mRNA expression levels of the MTA1, the human homologue of the rat mta1 gene in colorectal and gastric carcinomas and thus to evaluate the relevance of the expression of this gene to human carcinoma progression. The expression of MTA1 mRNA in 36 colorectal and 34 gastric carcinoma samples was compared with that in corresponding normal mucosa tissues by semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) and the results were compared with clinico-pathologic data. A relative overexpression of MTA1 mRNA (tumor/normal ratio > or = 2) was observed in 14 of 36 (38.9%) colorectal carcinomas and 13 of 34 (38.2%) gastric carcinomas. Clinico-pathologic correlations demonstrated that in colorectal carcinomas, tumors overexpressing MTA1 mRNA exhibited a significantly deeper wall invasion and a higher rate of metastasis to lymph nodes, and tended to be at an advanced Dukes' stage with frequent lymphatic involvement. In gastric carcinomas, the tumors overexpressing MTA1 mRNA showed significantly higher rates of serosal invasion and lymph node metastasis and tended to have a higher rate of vascular involvement. Our data suggest that overexpression of the MTA1 gene correlates with tumor invasion and the presence of metastases and that a high expression of MTA1 mRNA may be a potential indicator for assessing the malignant potential of colorectal and gastric carcinomas.
mta1基因是最近鉴定出的一个新的转移相关候选基因。推导的氨基酸序列包含一个src同源3结构域结合基序、一个锌指基序和可能的磷酸化位点，提示该基因参与信号转导或基因表达调控。我们研究的目的是检测MTA1（大鼠mta1基因的人类同源物）在结直肠癌和胃癌中的mRNA表达水平，从而评估该基因表达与人类肿瘤进展的相关性。通过半定量逆转录聚合酶链反应（RT-PCR）比较36例结直肠癌和34例胃癌样本中MTA1 mRNA的表达与相应正常黏膜组织中的表达，并将结果与临床病理数据进行比较。在36例结直肠癌中有14例（38.9%）、34例胃癌中有13例（38.2%）观察到MTA1 mRNA相对过表达（肿瘤/正常比值≥2）。临床病理相关性分析表明，在结直肠癌中，过表达MTA1 mRNA的肿瘤表现出明显更深的壁内浸润和更高的淋巴结转移率，且倾向于处于晚期杜克分期，伴有频繁的淋巴管受累。在胃癌中，过表达MTA1 mRNA的肿瘤表现出明显更高的浆膜侵犯率和淋巴结转移率，且倾向于有更高的血管受累率。我们的数据提示，MTA1基因的过表达与肿瘤侵袭和转移的存在相关，MTA1 mRNA的高表达可能是评估结直肠癌和胃癌恶性潜能的一个潜在指标。
