The role of erbB2 signal transduction pathways in human breast cancer

  title={The role of erbB2 signal transduction pathways in human breast cancer},
  author={Ruth Lupu and Marc E. Lippman},
  journal={Breast Cancer Research and Treatment},
SummaryThe erbB2 receptor is expressed at very high levels in nearly 30% of human breast cancer patients and plays an important role in the transformation and the prognosis of breast cancer. While evidence accumulates to support the relationship between erbB2 overexpression and poor overall survival in human breast cancer, understanding of the biological consequence(s) of erbB2 overexpression remains elusive. Our recent discovery, cloning, sequencing, and expression of the erbB2 ligand (gp30… 
The significance ofheregulin in breast cancer tumor progression and drug resistance
Heregulin is involved in breast cancer tumor progression and mechanistic aspects of theerbB-2/4 andheregulin interaction need to be understood from a therapeutic standpoint which could provide additional insights into synergistic treatments for certain patients, or improve treatment regimens for a large number of women.
Relationship between ERBB2 and E-cadherin expression in human breast cancer
Observations in different histological types of breast carcinoma strongly argue against a role for ERBB2 as a transcriptional regulator of E-CD expression in most human breast carcinomas in vivo.
Expression of erbB/HER receptors, heregulin and p38 in primary breast cancer using quantitative immunohistochemistry
The expression of EGFR, HER-2, heregulin, p38 and MAPK was independent of age, tumor size, number of lymph nodes involved or hormone receptor status, and the HER family of growth factor receptors appear to be regulated independently in invasive breast cancer.
Trastuzumab Plus Tamoxifen: Anti-Proliferative and Molecular Interactions in Breast Carcinoma
In ER-positive breast cancer cells overexpressing HER2, trastuzumab plus tamoxifen have antagonistic interactions when used in combination, and that this antagonism may be related with an increase in HER2 signaling pathways that occurs when tamox ifen is added to trastizumab.
Enhanced anti-proliferative activity of the combination of tamoxifen plus HER-2-neu antibody
An enhanced inhibitory effect on cell proliferation with the combination of Tamoxifen and the antibody compared to that seen by either agent alone is found.
Hormone receptor status does not affect the clinical benefit of trastuzumab therapy for patients with metastatic breast cancer.
The addition of trastuzumab to chemotherapy provides an improved clinical benefit compared with chemotherapy alone, regardless of HR status, and overall response rate (ORR) and time to progression (TTP) were significantly higher in patients treated with chemotherapy plus trastzumab than in those treated with cancer treatment alone.
Endocrine therapy and other targeted therapies for metastatic breast cancer
The most important change in the treatment of advanced breast cancer that will emerge over the next 10 years is the shift from adjuvant tamoxifen to adjuvant aromatase inhibitors. This will mean an
Heregulin inhibits proliferation via ERKs and phosphatidyl‐inositol 3‐kinase activation but regulates urokinase plasminogen activator independently of these pathways in metastatic mammary tumor cells
Assessment of the signaling pathways involved in HRGβ1 action indicated that the addition of HRG β1 to LM3 cells resulted in activation of phosphatidylinositol 3‐ kinase (PI‐3K) and in strong induction of the association of the p85 subunit of PI‐ 3K with ErbB‐3.
Heregulin-β1 regulates the estrogen receptor-α gene expression and activity via the ErbB2/PI 3-K/Akt pathway
Experiments employing selective ErbB inhibitors demonstrate that the effect of HRG-β1 on ER-α expression and activity is also mediated by Erb b2 and not by EGFR, demonstrating that ErbbB2 is the primary mediator of the effects of HRg- β1 onER-α regulation.


A ligand for the erbB-2 oncogene product (gp30) induces differentiation of human breast cancer cells.
  • S. Bacus, E. Huberman, R. Lupu
  • Biology
    Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
  • 1992
Findings indicate that ligand-induced growth inhibition in cells overexpressing erbB-2 is associated with an apparent induction of differentiation of cells with a more mature phenotype.
erbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells.
A new mechanism for acquisition of oncogenic properties by genes encoding growth factor receptor-like proteins is demonstrated and a functional basis for the role of their overexpression in the development of human malignancies is provided.
ERBB2 amplification in breast cancer with a high rate of proliferation.
It is concluded that ERBB2 activity is related to an increased tumor growth rate but not directly to metastasizing ability.
Direct interaction of a ligand for the erbB2 oncogene product with the EGF receptor and p185erbB2.
Evidence described here suggests that gp30 is a ligand for p185erbB2, a 185-kilodalton transmembrane protein whose sequence is similar to the epidermal growth factor receptor (EGFR).
Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.
Amplification of the HER-2/neu gene was a significant predictor of both overall survival and time to relapse in patients with breast cancer, and had greater prognostic value than most currently used prognostic factors in lymph node-positive disease.
Characterization of a growth factor that binds exclusively to the erbB-2 receptor and induces cellular responses.
The purification and characterization of a protein from SKBr-3 human breast cancer cells with a molecular mass of 75 kDa (p75) that is a p185erbB-2 ligand are reported, which show that SKBR-3 cells, which exhibit erbB- 2 amplification and overexpression, secrete a growth factor that binds and activates p 185erb B-2 specifically.
p185HER2 monoclonal antibody has antiproliferative effects in vitro and sensitizes human breast tumor cells to tumor necrosis factor.
It is shown that a monoclonal antibody directed against the extracellular domain of p185HER2 specifically inhibits the growth of breast tumor-derived cell lines overexpressing the HER2/c-erbB-2 gene product and prevents HER2-transformed NIH 3T3 cells from forming colonies in soft agar.
Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer.
The concept that the HER-2/neu gene may be involved in the pathogenesis of some human cancers, including breast and ovarian cancer, is supported.
Prognostic significance of c-erbB-2 and estrogen receptor status in human breast cancer.
Multivariate analysis indicated that the c-erbB-2 oncoprotein was an independent prognostic indicator for overall survival in breast carcinoma patients.