The use of gene transfer and recombinant DNA techniques has made it possible to identify a number of oncogenes that are active in human tumors and are presumably responsible for the altered properties of the tumor cells. Workers have identified a large number of these cellular oncogenes as well as oncogenes of viral origin. A main goal of the proposed work is to understand how the actions of these various oncogenes may be integrated into a scheme that describes the growth regulatory networks of the cell. Some of these oncogenes have been found to collaborate with others in tumorigenic conversion of cells. This has allowed a classification of some into a functional group characterized by having properties similar to the ras oncogenes. The paradigm of the second group is the myc oncogene. Proposed work will undertake to analyze the nature of other oncogenes. A second scheme by which oncogenes may be understood stems from the principle that these genes confer on the cell an autonomy from normally required growth factors. Such oncogenes may provide the cell with its own growth factors. Proposed experiments will investigate whether a growth factor gene can be activated into an oncogene. Alternatively, growth factor autonomy may be achieved by alterations in a cellular growth factor receptor. Proposed experiments will examine an oncogene protein that appears to function as a growth factor receptor. Other experiments will study ras p21 proteins that may transmit growth stimuatory signals sent out by the receptors. Longer term experiments will examine tumor genes that enable cells to metastasize or escape immune surveillance.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Unknown (R35)
Project #
2R35CA039826-08
Application #
3479120
Study Section
Special Emphasis Panel (SRC (88))
Project Start
1985-08-01
Project End
1999-07-31
Budget Start
1992-08-28
Budget End
1993-07-31
Support Year
8
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Whitehead Institute for Biomedical Research
Department
Type
DUNS #
076580745
City
Cambridge
State
MA
Country
United States
Zip Code
02142
Schratt, G; Weinhold, B; Lundberg, A S et al. (2001) Serum response factor is required for immediate-early gene activation yet is dispensable for proliferation of embryonic stem cells. Mol Cell Biol 21:2933-43
Liu, X; Sun, Y; Weinberg, R A et al. (2001) Ski/Sno and TGF-beta signaling. Cytokine Growth Factor Rev 12:1-8
Brisken, C; Heineman, A; Chavarria, T et al. (2000) Essential function of Wnt-4 in mammary gland development downstream of progesterone signaling. Genes Dev 14:650-4
Sun, Y; Liu, X; Ng-Eaton, E et al. (1999) SnoN and Ski protooncoproteins are rapidly degraded in response to transforming growth factor beta signaling. Proc Natl Acad Sci U S A 96:12442-7
Geng, Y; Whoriskey, W; Park, M Y et al. (1999) Rescue of cyclin D1 deficiency by knockin cyclin E. Cell 97:767-77
Sun, Y; Liu, X; Eaton, E N et al. (1999) Interaction of the Ski oncoprotein with Smad3 regulates TGF-beta signaling. Mol Cell 4:499-509
Counter, C M; Hahn, W C; Wei, W et al. (1998) Dissociation among in vitro telomerase activity, telomere maintenance, and cellular immortalization. Proc Natl Acad Sci U S A 95:14723-8
Kolquist, K A; Ellisen, L W; Counter, C M et al. (1998) Expression of TERT in early premalignant lesions and a subset of cells in normal tissues. Nat Genet 19:182-6
Brisken, C; Park, S; Vass, T et al. (1998) A paracrine role for the epithelial progesterone receptor in mammary gland development. Proc Natl Acad Sci U S A 95:5076-81
Medema, R H; Klompmaker, R; Smits, V A et al. (1998) p21waf1 can block cells at two points in the cell cycle, but does not interfere with processive DNA-replication or stress-activated kinases. Oncogene 16:431-41

Showing the most recent 10 out of 58 publications