Molecular Analysis of Motility in Metastatic Mammary Adenocarcinoma Cells
Final rept. 26 Aug 94-25 Aug 98
ALBERT EINSTEIN COLL OF MEDICINE BRONX NY
Pagination or Media Count:
This final report provides 1 a detailed account of our analysis of the role of the Arp23 complex in mediating EGF-stimulated lamellipod extension, 2 a description of our results in producing cell lines expressing talin anti-sense RNA, and 3 a general summary of our understanding of the process of lamellipod extension in mammary adenocarcinoma cells, based upon the work supported by this grant. We find that the Arp 23 complex is present in parallel with filamentous actin at the leading edge. This localization is much broader that the distribution of EGF-stimulated nucleation sites and is more consistent with the Arp 23 complex fincfloning as a pointed end capper. We have produced cells expressing talin antisens niRNA which show a regulated 50 decrease in the amount of talin protein. The cells show reduced focal contacts and altered stress fiber distributions. However, BOF-stimulated lamellipod extension is not quantitatively altered. Talin localization to the leading edge appears to be tighter than localization to focal contacts. In summary, our results show that ECiF stimulation of tumor cells produces a highly localized increase in actin nucleation within 100 nm of the membrane that is independent of interaction with the substratum.
- Anatomy and Physiology
- Medicine and Medical Research