Accession Number : ADA300382

Title :   Expression of the Epidermal Growth Factor Receptor Family in Transgenic Mouse Models of Human Breast Cancer.

Descriptive Note : Annual rept. 1 Aug 94-31 Jul 95,

Corporate Author : MCMASTER UNIV HAMILTON (ONTARIO)

Personal Author(s) : Muller, William J.

PDF Url : ADA300382

Report Date : 19 AUG 1995

Pagination or Media Count : 38

Abstract : Transgenic mice expressing either the neu or TGFa in the mammary epithelium develop focal mammary tumours that occur only after a long latency period. Because the epidermal growth factor receptor and Neu are capable of forming eterodimers that are responsive to EFGR ligands such as TGFa, we examined whether Neu and TGFa could cooperate to accelerate the onset of mammary tumours. To accomplish this objective we have interbred separate strains harbouring either a MMTV/TGFoc or MMTV/neu transgenes to generate bitransgenic mice coexpressing both Neu and TGFa. The results revealed that by contrast to either parental strain, female mice coexpressing TGFa and Neu in the mammary epithelium develop multi focal mammary tumours which arise after a short latency period. The rapid induction of mammary tumours in these bitransgenic mice is further correlated with the tyrosine phosphorylation of both Neu and EGFR. Moreover, in established cell lines overexpressing EGFR, EGF stimulation results in the transphosphorylation of the Neu and the formation of complexes between c-Src and tyrosine phosphorylated Neu. Taken together these observations suggest that Neu and EGFR cooperate by recruiting distinct but complementary signalling pathways.

Descriptors :   *MAMMARY GLANDS, *GROWTH(PHYSIOLOGY), *BREAST CANCER, STIMULATION(GENERAL), HUMANS, RECRUITING, SIGNALS, LIGANDS, MICE, INDUCTION SYSTEMS, SENSE ORGANS, FEMALES, EPIDERMIS, TYROSINE, PHOSPHORYLATION.

Subject Categories : Biology
      Anatomy and Physiology

Distribution Statement : APPROVED FOR PUBLIC RELEASE