Albertazzi E, Cajone F, Leone B E, Naguib R N, Lakshmi M S, Sherbet G V
Department of Pathology, Centro Di Studio Sulla Patologia Cellulare Del CNR, University of Milan, Italy.
DNA Cell Biol. 1998 Apr;17(4):335-42. doi: 10.1089/dna.1998.17.335.
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.
小鼠的18A2/mts1及其人类同源物h-mts1（S100A4）编码一种属于S-100家族的钙结合蛋白，与小鼠肿瘤、体外培养的人类肿瘤细胞系以及异种移植生长的人类肿瘤的高侵袭和转移潜能相关。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能呈负相关。这两个人类基因的产物都改变细胞骨架动力学，且具有拮抗作用。鉴于nm23与人类癌症转移潜能的关联不明确，我们怀疑h-mts1和nm23的相对表达可能比单独的任何一个基因更准确地反映肿瘤进展。我们在此描述这些基因在乳腺浸润性导管癌中的表达，并表明h-mts1高表达与区域淋巴结转移扩散相关。nm23自身的表达与淋巴结扩散没有统计学上的显著负相关。然而，这两个基因的表达状态综合起来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雌激素和孕激素受体呈阳性。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以及类固醇受体的表达状态和h-mts1与nm23基因的表达水平，以预测癌的淋巴结扩散的准确性。这些分析支持这样的结论，总体而言，h-mts1表达似乎与更具侵袭性的疾病相关并可作为其指标。与nm23互补，h-mts1可以成为乳腺癌预后的有力标志物。
