Moustafa A S, Nicolson G L
Institute for Molecular Medicine, Huntington Beach, CA 92649, USA.
Oncol Res. 1997;9(10):505-25.
The metastatic spread of breast cancer accounts for most of its morbidity and mortality; therefore, identifying the genes and gene products involved in breast cancer metastasis formation should be useful for better diagnosis, prognosis, treatment, and follow-up of patients with metastatic breast cancer. Unfortunately, little is known about these genes or the functions of their encoded products. Abnormalities in at least three broad gene categories (oncogenes, regulatory genes or effector genes, and tumor-suppressor genes) have been shown to contribute to the origin and/or progression of breast neoplasias. Such abnormalities are mainly manifested by quantitative changes in gene expression, resulting in loss of normal cellular regulation and enhanced cellular diversification. In addition, qualitative genetic alterations, such as gene amplifications and mutations, may also be involved in breast cancer progression. The role(s) of different breast cancer metastasis-associated genes, if known, in the complex multistep process of invasion and metastasis is discussed along with studies that have identified new molecular probe(s) that may be useful in predicting metastasis formation and outcome in breast cancer and for selecting candidates for adjuvant therapy. Understanding the genetic and thus molecular basis of metastasis formation should also provide important insights on the development of new therapeutic approaches for treatment of metastatic breast cancers based on gene targeting and repair of genetic defects that control metastatic properties.
乳腺癌的转移扩散是其发病和死亡的主要原因；因此，鉴定参与乳腺癌转移形成的基因及其产物，对于转移性乳腺癌患者的更好诊断、预后评估、治疗及随访应是有益的。遗憾的是，对于这些基因及其编码产物的功能知之甚少。至少三类广泛的基因（癌基因、调节基因或效应基因以及肿瘤抑制基因）异常已被证明与乳腺肿瘤的发生和/或进展有关。此类异常主要表现为基因表达的定量变化，导致正常细胞调控丧失及细胞多样性增强。此外，基因扩增和突变等定性遗传改变也可能参与乳腺癌进展。文中讨论了不同的乳腺癌转移相关基因（若已知）在复杂的侵袭和转移多步骤过程中的作用，同时还提及了已鉴定出可能有助于预测乳腺癌转移形成和预后以及选择辅助治疗候选者的新分子探针的研究。了解转移形成的遗传及分子基础，也应为基于基因靶向和修复控制转移特性的遗传缺陷来开发转移性乳腺癌新治疗方法提供重要见解。
