Accession Number : ADA319828

Title :   Int-3 Oncogene in Normal and Neoplastic Breast Development.

Descriptive Note : Annual rept. 1 Sep 95-31 Aug 96,

Corporate Author : COLUMBIA UNIV NEW YORK

Personal Author(s) : Kitajewski, Jan

PDF Url : ADA319828

Report Date : SEP 1996

Pagination or Media Count : 36

Abstract : We have cloned and sequenced the full length int-3 gene and have renamed it Notch4, since it is the fourth vertebrate Notch gene identified. The protein encoded by Notch4 is a 220 kilodalton cell surface receptor. Notch4 is a bona fide Notch receptor with 29 EOF-like repeats, 3 Notchllin- 12 repeats, and an intracellular domain with ankyrin repeats. Notch4 is expressed primarily in the adult and embryonic endothelium. Activation of Notch4, to the int-3 oncoprotein, results in a truncated receptor lacking the extracellular domain but retaining the transmembrane and intracellular domains. Notch4 receptors are membrane associated, as expected for cell surface receptors; whereas the int-3 oncoprotein resides in the nucleus. Activated int-3 can block hepatocyte growth factor induced ductal morphogenesis of an established normal human mammary epithelial cell line, TAC-2. Int-3 does not stimulate increased cell growth of TAC-2 cells. The ability of int-3 to block morphogenesis resembles its function in oncogenesis in the mammary gland.

Descriptors :   *NEOPLASMS, *VERTEBRATES, *EMBRYOS, *MAMMARY GLANDS, *BREAST CANCER, GENES, CLONES, LIVER, CELLS(BIOLOGY), SENSE ORGANS, TRUNCATION, ENDOTHELIUM, GROWTH(PHYSIOLOGY).

Subject Categories : Medicine and Medical Research
      Toxicology

Distribution Statement : APPROVED FOR PUBLIC RELEASE