ELONGATION FACTOR-I-ALPHA IS AN OVEREXPRESSED ACTIN-BINDING PROTEIN IN METASTATIC RAT MAMMARY ADENOCARCINOMA

Overexpression of elongation factor-1 alpha (EF1 alpha) mRNA has been correlated with increased metastatic potential in mammary adenocarcino ma; however, this relationship was not explored at the level of protei n expression, As EF1 alpha has been shown in other cell types to be a component of the actin cytoskeleton, a likely effector in metastasis, the actin binding activity of EF1 alpha from metastatic and nonmetasta tic rat breast tumors and cell lines was investigated, We have shown t hat EF1 alpha protein is overexpressed in metastatic compared to nonme tastatic cells and whole tumors, Similarly to other EF1 alpha s, both types of tumor EF1 alpha bind to F-actin, but EF1 alpha from metastati c cells has a reduced affinity for actin, In addition, there is a high correlation between the intracellular distribution of filamentous act in and EF1 alpha in those cytoskeletal structures thought to be import ant for supporting the cellular motility required for metastasis, Foll owing stimulation with EGF, there is a parallel increase in the amount of F-actin and EF1 alpha associated with the cytoskeleton, The respon se to EGF can be blocked with cytochalasin D indicating that the bindi ng of EF1 alpha to the cytoskeleton is mediated by F-actin, We propose that a weakened association of EF1 alpha with actin may be related to the metastatic process via an altered organization of the actin cytos keleton and the differential translation of mRNAs associated with the cytoskeleton.