Expression of metastasis-associated genes h-mtsl (S100A4) and nm23 in carcinoma of breast is related to disease progression
Expression of metastasis-associated genes h-mtsl (S100A4) and nm23 in carcinoma of breast is related to disease progression
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DOI：
10.1089/dna.1998.17.335
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发表时间：
1998-04-01
影响因子：
3.1
通讯作者：
Sherbet, GV
中科院分区：
文献类型：
--
作者：
Albertazzi, E;Cajone, F;Sherbet, GV
小鼠18A2/mts1及其人类同源基因h-mts1 （S100A4）编码一种属于S-100家族的Ca2+结合蛋白，与小鼠肿瘤、体外人类肿瘤细胞系和异种移植物生长的人类肿瘤的高侵袭性和转移性有关。nm23是一种假定的转移抑制基因，其表达已被发现与某些形式的人类癌症的转移潜力呈负相关。这两种人类基因的产物改变了细胞骨架动力学，具有拮抗作用。鉴于nm23与人类癌症转移潜能的关系不明确，我们怀疑h-mts1和nm23的相对表达可能比它们单独表达更准确地反映肿瘤的进展。我们在此描述了这些基因在乳腺浸润性导管癌中的表达，并表明高h-mts1表达与转移扩散到区域淋巴结有关。nm23单独表达与淋巴结扩散无显著负相关。然而，这两个基因的表达状态，加在一起，与淋巴结转移的发生密切相关。未检测到h-mts1表达的乳腺癌被发现是雌激素和孕激素受体阳性。h-mts1的表达与肿瘤分化无关。利用人工神经网络分析临床数据，结合类固醇受体的表达状态以及h-mts1和nm23基因的表达水平，以预测肿瘤淋巴结转移的准确性。这些分析支持这样的结论，即总的来说，h-mts1的表达似乎与更具侵袭性的疾病有关。与nm23互补，h-mts1可作为乳腺癌预后的有力指标。
The murine 18A2/mts1 and its human homolog h-mts1 (S100A4), encoding a Ca2+-binding protein belonging to the S-100 family, are associated with high invasive and metastatic potentials of murine tumors, human tumor cell lines in vitro, and human tumors growing as xenografts. The nm23 is a putative metastasis-suppressor gene whose expression has been found to correlate inversely with the metastatic potential of some forms of human cancer. The products of both human genes alter cytoskeletal dynamics, with antagonistic effects. In view of the equivocal association of nm23 with the metastatic potential of human cancer, we suspected that the relative expression of h-mts1 and nm23 might reflect tumor progression more accurately than either of them alone. We describe here the expression of these genes in infiltrating ductal carcinomas of the breast and show that high h-mts1 expression is associated with metastatic spread to the regional lymph nodes. The expression of nm23 on its own did not show a statistically significant inverse correlation with nodal spread. However, the expression status of the two genes, taken together, correlated strongly with the occurrence of nodal metastases. Breast cancers with no detectable expression of h-mts1 were found to be estrogen and progesterone receptor positive. Expression of h-mts1 was not related to tumor differentiation. The clinical data, together with the state of expression of steroid receptors and the expression levels of h-mts1 and nm23 genes, were analyzed using artificial neural networks for accuracy in predicting nodal spread of the carcinomas. These analyses support the conclusion that, overall, h-mts1 expression appears to be associated with and indicative of more aggressive disease. Complemented with nm23, h-mts1 could provide a powerful marker of breast cancer prognosis.