My laboratory has described a new gene family in mammalian cells. Transcription of this gene family is coordinately induced by platelet-derived growth factor (PDGF) in Balb/c-3T3 cells. We have isolated five representative members of this gene family (which we term """"""""competence"""""""") by molecular cloning techniques. We have shown that at least two proto-oncogenes (c-myc and c-fos) are contained within the family. Some if not all, of the competence gene products function as positive intracellular mediators of the growth response to PDGF. During the course of this work, we also observed rare gene sequences whose expression is suppressed by PDGF. We suspect that these gene products may function as negative growth regulators. Specifically, genes which are suppressed by PDGF may serve to initiate and maintain the Go growth arrest state. The research described in this application has three objectives. The first objective is isolation and molecular characterization of PDGF-suppressible gene sequences. The genes will be isolated as full length cDNA clones. Towards this end we have updated and improved the differential colony hybridization protocol used to isolate the original competence genes. The second objective is to identify the translation products of these PDGF-suppressible genes. We will express the genes in bacteria and raise antisera to the expressed proteins. These antisera will be used to determine the subcellular location of PDGF-suppressible proteins. The nucleic acid sequence of the genes will be determined and then screened for homologies to other genes using computer matching techniques. The final objective is to determine whether these PDGF-suppressible genes inhibit the mitogenic response of normal 3T3 cells to serum and serum growth factors. This objective will be approached by transfecting the genes into 3T3 cells under control of a steroid inducible promoter element.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM031489-06
Application #
3279520
Study Section
Molecular Biology Study Section (MBY)
Project Start
1983-02-01
Project End
1991-01-31
Budget Start
1988-02-01
Budget End
1989-01-31
Support Year
6
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115
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Segal, R A; Pomeroy, S L; Stiles, C D (1995) Axonal growth and fasciculation linked to differential expression of BDNF and NT3 receptors in developing cerebellar granule cells. J Neurosci 15:4970-81
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Zumstein, P; Stiles, C D (1987) Molecular cloning of gene sequences that are regulated by insulin-like growth factor I. J Biol Chem 262:11252-60

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