Previous efforts to study interactions of metastatically potent cells with components of extracellular matrix and with endothelial cells continued. To this end the cell fractionation study of cultured human melanoma cells was performed. Differential intracellular localization of 37 kD putative laminin receptor precursor and its 67 kDa mature from protein was shown. The integrin expression on the surface of prostate cancer cells with different tumorigenicity and metastatic potency was investigated. The role of the particular integrins in the interactions with endothelial cells receptors was also in the focus of our research. The role of RGD binding integrins in the development of acute renal failure was studied in cooperation with Division of Nephrology from New York State University at Stony Brook. The role of phosphorylated proteins in integrin dependent apoptosis was investigated in cultured renal epithelial cells. In collaboration with Dr. Zolotukhin and Dr. Felber we studied the functions of different regulatory elements in dynamic distribution of HIV gag mRNA in transfected cells. Previous work continued towards the understanding the effects of proto-oncogene on the normal development and tumorgenesis. We found that mouse embryonic fibroblasts (MEF's) lacking the -53 tumor suppressor protein, multiple copies of functionally competent centrosomes are generated during a single cell cycle which profoundly affect mitotic fidelity, and suggest one possible mechanism by which the loss of p53 may cause genetic instability. For the mos proto-oncogene study, we found that, by using mouse oocyte, Mos/MAPK (mitogen-active protein kinase) can induce the formation of multiple microtubule arrays, which appear to nucleate from condensing chromatin in and around the GV (germinal vesicle). Also, large holes develop in the GV, which are adjacent to condensed chromatin. By causing a substantial delay in the GVBD and metaphase of meiosis I, our technique permits the detailed analysis of the early stages of meiosis I. For the met proto-oncogene, we found that hepatocyte growth factor/scatter factor-met signaling induces proliferation, migration and ductual morphogenesis of pancreatic oval cells. For the human lung cancer the Met protein was highly expressed in the adenocarcinoma, for the mesothelioma, the Met was highly expressed in the epithelial cell components which suggesting the involvement of Met protein in the epithelial development.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC008387-09
Application #
2463738
Study Section
Special Emphasis Panel (LMMB)
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
1996
Total Cost
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code