GENISTEIN-STIMULATED ADHERENCE OF PROSTATE-CANCER CELLS IS ASSOCIATEDWITH THE BINDING OF FOCAL ADHESION KINASE TO BETA-1-INTEGRIN

The isoflavinoid genistein is a protein-tyrosine kinase inhibitor whic h has been identified as a putative cancer prevention agent, Its consu mption is associated with a low incidence of clinical metastatic prost ate cancer in the face of a sustained high incidence of organ-confined prostate cancer, We therefore undertook studies to examine genistein' s effect upon tell adhesion as one possible mechanism by which it coul d be acting as an antimetastatic: agent, A morphogenic analysis reveal ed that genistein caused cell flattening in a variety of cell lines: P C3-M, PC3, and DU-145 prostate carcinoma cells, as well as MCF-7 breas t carcinoma cells, Mechanistic studies focused on the highly metastati c PC3-M cell Line, and revealed that cell flattening was accompanied b y an increase in cell adhesion, Further investigations demonstrated th at focal adhesion kinase (FAK) accumulated in areas of focal cell atta chment, and that this accumulation occurred only when cells were activ ely undergoing genistein-mediated morphologic change, Concurrent forma tion of a complex between the cell attachment molecule, beta-1-integri n, and FAK was shown to occur, and to correlate with transient activat ion of FAK activity, Genistein is presented as a novel investigative t ool for use in the study of molecular events involved in the process o f cell adhesion.