Accession Number:

ADA455755

Title:

Determine the Mechanism by Which Specific ErbB Receptor Dimers Differ in Their Ability to Disrupt Epithelial Cell Polarity

Descriptive Note:

Annual summary 1 Apr 2003-31 Mar 2006

Corporate Author:

COLD SPRING HARBOR LAB NY

Report Date:

2006-04-01

Pagination or Media Count:

11.0

Abstract:

Loss of epithelial architecture is thought to be an early event in carcinoma. The mechanism by which oncogenes disrupt epithelial architecture is poorly understood. Previous results from our lab have shown that ErbB2, an oncogene correlated to poor clinical prognosis in breast cancer, can disrupt epithelial cell polarity. My research is aimed at investigating how activation of ErbB2 disrupts epithelial cell polarity. Activation of ErbB2 is known to induce phosphorylation of five tyrosines in its cytoplasmic tail. Using ErbB2 autophosphorylation site mutants I investigated whether a particular tyrosine residue mediates the ErbB2-induced changes in epithelial cell polarity. In mammary epithelial cells grown as three-dimensional 3D structures, Yi 144, Yl2Ol, Y122617 and Y1253 were all sufficient to disrupt the structural architecture when activated during the process of morphogenesis. However, if these same sites were activated after structures were fully formed they were unable to disrupt the acinar architecture. It therefore appears that in fully organized three-dimensional structures more than one tyrosine site is needed to disrupt architecture, whereas in developing structures one site is sufficient.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE