Disclosed are DNA sequences encoding novel DNA binding proteins implicated in regulation of early stages of cell growth. Illustratively provided are human and mouse origin DNA sequences encoding early growth regulatory ("Egr") proteins which include "zinc finger" regions of the type involved in DNA binding. Also disclosed are immunological methods and materials for detection of Egr proteins and hybridization methods and materials for detection and quantification of Egr protein related nucleic acids.
CROSS-REFERENCE TO RELATED APPLICATIONS
This is a continuation-in-part application of co-pending U.S. patent application Ser. No. 179,587, filed Apr. 8, 1988 now abandoned.
This invention is directed to methods for inhibiting the growth in vitro or in an individual of a tumor cell induced by the mitogenic activity of PDGF by transfecting the cell with an expression vector having an expression control sequence operatively linked to a nucleic acid sequence encoding a mammalian EGR, a nucleic acid sequence encoding a fragment of a mammalian EGR comprising the three zinc fingers or a nucleic acid sequence that hybridizes to any of the foregoing nucleic acid sequences under standard hybridization conditions and that encodes a polypeptide having the cell growth-inhibiting activity of Egr-1.
The invention relates to the use of an Egr-1 transcription factor polypeptide or a biologically active fragment thereof, and to nucleic acid molecules encoding such polypeptides, in the manufacture of a medicament for the treatment of wounds in a mammal, including human. In addition, it relates to a sequence that is believed to include important regions involved in the transcription of the transcription factor Egr-1 in humans and in the regulation thereof. This sequence can be used to design appropriate nucleic acid molecules and vectors that can be used in the treatment of wounds, as well as in other treatment.
The present invention provides a method of inhibiting the proliferation of cells. The method comprises inhibiting induction or decreasing expression of Egr-1 or decreasing the nuclear accumulation or activity of the Egr-1 gene product. The present invention also provides a method of reducing the incidence of restenosis in a subject. The method comprises administering to the subject an agent which inhibits induction or decreases expression of Egr-1 or decreases the nuclear accumulation or activity of the Egr-1 gene product.
Disclosed are DNA sequences encoding novel DNA binding proteins implicated in regulation of early stages of cell growth. Illustratively provided are human and mouse origin DNA sequences encoding early growth regulatory ("Egr") proteins which include "zinc finger" regions of the type involved in DNA binding. Also disclosed is a detailed analysis of the structure and function of the early growth regulatory protein, Egr-1, delineating independent and modular activation, repression, DNA-binding, and nuclear localization activities. Also disclosed are immunological methods and materials for detection of Egr proteins and hybridization methods and materials for detection and quantification of Egr protein related nucleic acids.
This invention relates to genetic constructs which comprise an enhancer-promoter region which is responsive to radiation, and at least one structural gene whose expression is controlled by the enhancer-promoter. This invention also relates to methods of destroying, altering, or inactivating cells in target tissue by delivering the genetic constructs to the cells of the tissues and inducing expression of the structural gene or genes in the construct by exposing the tissues to ionizing radiation. This invention is useful for treating patients with cancer, clotting disorders, myocardial infarction, and other diseases for which target tissues can be identified and for which gene expression of the construct within the target tissues can alleviate the disease or disorder.
