Bergan R, Kyle E, Nguyen P, Trepel J, Ingui C, Neckers L
Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda 20892, MD, USA.
Clin Exp Metastasis. 1996 Sep;14(4):389-98. doi: 10.1007/BF00123398.
The isoflavinoid genistein is a protein-tyrosine kinase inhibitor which has been identified as a putative cancer prevention agent. Its consumption is associated with a low incidence of clinical metastatic prostate cancer in the face of a sustained high incidence of organ-confined prostate cancer. We therefore undertook studies to examine genistein's effect upon cell adhesion as one possible mechanism by which it could be acting as an antimetastatic agent. A morphogenic analysis revealed that genistein caused cell flattening in a variety of cell lines: PC3-M, PC3, and DU-145 prostate carcinoma cells, as well as MCF-7 breast carcinoma cells. Mechanistic studies focused on the highly metastatic PC3-M cell line, and revealed that cell flattening was accompanied by an increase in cell adhesion. Further investigations demonstrated that focal adhesion kinase (FAK) accumulated in areas of focal cell attachment, and that this accumulation occurred only when cells were actively undergoing genistein-mediated morphologic change. Concurrent formation of a complex between the cell attachment molecule, beta-1-integrin, and FAK was shown to occur, and to correlate with transient activation of FAK activity. Genistein is presented as a novel investigative tool for use in the study of molecular events involved in the process of cell adhesion.
异黄酮染料木黄酮是一种蛋白质酪氨酸激酶抑制剂，已被确定为一种潜在的癌症预防剂。尽管器官局限性前列腺癌的发病率持续居高不下，但食用染料木黄酮与临床转移性前列腺癌的低发病率相关。因此，我们开展了研究，以检验染料木黄酮对细胞黏附的影响，这是其作为抗转移剂可能发挥作用的一种机制。形态学分析表明，染料木黄酮可导致多种细胞系发生细胞扁平化：PC3-M、PC3和DU-145前列腺癌细胞，以及MCF-7乳腺癌细胞。机制研究聚焦于高转移性PC3-M细胞系，结果显示细胞扁平化伴随着细胞黏附的增加。进一步研究表明，粘着斑激酶（FAK）在细胞粘着斑区域积聚，且这种积聚仅在细胞积极经历染料木黄酮介导的形态变化时发生。同时发现，细胞黏附分子β-1整合素与FAK之间形成了复合物，且与FAK活性的短暂激活相关。染料木黄酮是一种新型研究工具，可用于研究细胞黏附过程中涉及的分子事件。
