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Updated: Jul 13, 2026

Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer
07:45

Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer

Published on: May 18, 2020

Distinct ErbB-2 coupled signaling pathways promote mammary tumors with unique pathologic and transcriptional profiles

Babette Schade1, Sonya H L Lam, Daniela Cernea

  • 1Molecular Oncology Group, McGill University Health Centre, McGill University, Montreal, Quebec, Canada.

Cancer Research
|August 19, 2007
PubMed

Insights

Different ErbB-2 signaling pathways impact breast cancer progression. The Neu-YB pathway drives aggressive, metastatic tumors with unique gene expression, unlike other ErbB-2 sites.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • ErbB-2 (Human Epidermal growth factor Receptor 2) overexpression is common in breast cancer, linked to poor prognosis.
  • Specific tyrosine-autophosphorylation sites in ErbB-2's cytoplasmic tail recruit different adaptor proteins and mediate transforming signals.
  • Previous studies identified growth factor receptor binding protein 2 (Grb2; Neu-YB) and Src homology and collagen (Shc; Neu-YD) binding sites as inducers of mammary tumorigenesis and metastasis.

Purpose of the Study:

  • To investigate the role of the remaining two ErbB-2 autophosphorylation sites (Neu-YC and Neu-YE) in mammary tumor development.
  • To compare the biological and transcriptional profiles of mouse models with different ErbB-2 autophosphorylation site mutations.

Main Methods:

  • Generation of transgenic mouse models expressing specific ErbB-2 autophosphorylation site mutants (Neu-YC, Neu-YE, Neu-YB).
  • Pathological and transcriptional analysis of mammary tumors developed in these mouse models.
  • Comparison of gene expression profiles, focusing on genes associated with tumor progression.

Main Results:

  • Transgenic mice with Neu-YC and Neu-YE sites developed metastatic mammary tumors with shared pathological and transcriptional features.
  • The Neu-YB mouse model exhibited unique pathology and high metastatic potential, associated with a distinct transcriptional profile.
  • Upregulated genes in Neu-YB tumors included metalloproteinases and chemokines, promoting malignant progression.
  • Neu-YB tumor cells showed high intracellular levels of chemokine CXCL12/SDF-1alpha, suggesting aggressive behavior.

Conclusions:

  • Distinct ErbB-2 autophosphorylation sites activate different signaling pathways.
  • These distinct pathways significantly influence the biological behavior and metastatic potential of ErbB-2-induced mammary tumors.
  • The Neu-YB pathway is particularly linked to aggressive tumor progression and metastasis in breast cancer models.

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