Role for HER2/neu and HER3 in fulvestrant-resistant breast cancer.

Role for HER2/neu and HER3 in fulvestrant-resistant breast cancer. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Role for HER2/neu and HER3 in fulvestrant-resistant breast cancer. Abstract Text:

Clodia Osipo,Kathleen Meeke,Dong Cheng,Alyssa Weichel,Anne Bertucci,Hong Liu,V Craig Jordan,

Tamoxifen resistance is common for estrogen receptor alpha (ERalpha) positive breast cancer. Second-line therapies include aromatase inhibitors or fulvestrant. We have shown previously that fulvestrant reversed 17beta-estradiol-induced tumor regression of tamoxifen-stimulated MCF-7 xenografts (MCF-7TAMLT) treated for >5 years with tamoxifen in athymic mice and paradoxically stimulated growth. We investigated mechanisms responsible for growth by fulvestrant in the presence of physiologic estradiol and therapeutic strategies in vivo. The results demonstrated that only estradiol increased expression of the estrogen-responsive genes, c-myc, igf-1, cathepsin D, and pS2 mRNAs, in MCF-7E2 and MCF-7TAMLT tumors. Tamoxifen or fulvestrant decreased the estradiol-induced increase of these mRNAs in both tumor models. However, tyrosine-phosphorylated HER2/ neu, HER3, phospho-extracellular-regulated kinase-1/2 (ERK-1/2), and phospho-glycogen synthetase kinase 3alpha (GSK3alpha) and beta proteins were increased in MCF-7TAMLT tumors treated with fulvestrant compared to estradiol, control, or tamoxifen. Phospho-HER2/neu interacted with HER3 protein in MCF-7TAMLT tumors. In order to determine whether the functional interaction of HER2/neu with HER3 is critical for growth of fulvestrant-stimulated MCF-7TAMLT tumors, pertuzumab (an antibody that blocks HER2/neu-HER3 interaction) was used in an in vivo xenograft growth assay. Only growth of fulvestrant-treated MCF-7TAMLT xenografts was decreased significantly by 37.2% in response to pertuzumab (P=0.004). Pertuzumab specifically decreased the interaction of HER2/neu protein with HER3 in fulvestrant-stimulated MCF-7TAMLT tumors. These results suggested growth of MCF-7TAMLT tumors by tamoxifen or fulvestrant is potentially independent of ERalpha transcriptional activity as evidenced by lack of induction of four estrogen-responsive genes. The results suggested that growth of MCF-7TAMLT tumors treated with fulvestrant in the presence of physiologic estradiol is in part mediated through enhanced signaling from the HER2/neu-HER3 pathway as pertuzumab partially inhibited growth and the interaction of HER2/neu with HER3 in vivo.

Role for HER2/neu and HER3 in fulvestrant-resistant breast cancer. Publishing Authors By Initials

C Osipo,K Meeke,D Cheng,A Weichel,A Bertucci,H Liu,VC Jordan,

For similar organic chemicals: hydrocarbons: hydrocarbons, cyclic: hydrocarbons, aromatic: benzene derivatives: benzylidene compounds: stilbenes: tamoxifen research abstracts see: organic chemicals: hydrocarbons: hydrocarbons, cyclic: hydrocarbons, aromatic: benzene derivatives: benzylidene compounds: stilbenes: tamoxifen research

PUBMED ID PMID:

MEDLINE DATE:

Role for HER2/neu and HER3 in fulvestrant-resistant breast cancer. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: International journal of oncology

VOLUME: 30

Page Numbers: 509-20

Journal Abbreviation: Int. J. Oncol.

ISSN: 1019-6439

DAY: 3

MONTH: Feb

YEAR: 2007

Role for HER2/neu and HER3 in fulvestrant-resistant breast cancer. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9306042

Role for HER2/neu and HER3 in fulvestrant-resistant breast cancer. Keywords Mesh Terms:

KEYWORDS: Tamoxifen

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Role for HER2/neu and HER3 in fulvestrant-resistant breast cancer. Information

Substance Name: Receptor, erbB-3

Registry Number: EC 2.7.1.112

Grant and Affiliation Information for Role for HER2/neu and HER3 in fulvestrant-resistant breast cancer.

AFFILIATION: Department of Pathology, Oncology Institute, Cardinal Bernadin Cancer Center, Loyola University Medical Center, Maywood, IL, USA.

Country: Greece

AGENCY: United States NCI

GRANT: CA89018-05

ACRONYM: CA

MEDLINETA: Int J Oncol

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Role for HER2/neu and HER3 in fulvestrant-resistant breast cancer Related Publications

• 2-Methoxyestradiol suppresses microtubule dynamics and arrests mitosis without depolymerizing microtubules.
• A laser-temperature-jump method for the study of the rate of transfer of hydrophobic ions and carriers across the interface of thin lipid membranes.
• Acetylphosphinate is the most potent mechanism-based substrate-like inhibitor of both the human and Escherichia coli pyruvate dehydrogenase components of the pyruvate dehydrogenase complex.
• Androgen-sensitivity of somata and dendrites of spinal nucleus of the bulbocavernosus (SNB) motoneurons in male C57BL6J mice.
• Beyond raloxifene for the prevention of osteoporosis and breast cancer.
• Cooperative effect of gefitinib and fumitremorgin c on cell growth and chemosensitivity in estrogen receptor alpha negative fulvestrant-resistant MCF-7 cells.
• Current noise in transport of hydrophobic ions through lipid bilayer membranes including diffusion polarization in the aqueous phase.
• Development of a one-step immunocapture real-time TaqMan RT-PCR assay for the broad spectrum detection of Pepino mosaic virus.
• Dexamethasone in acute bacterial meningitis.
• Effect of raloxifene on salivary sex steroid concentrations in premenopausal women.
• Effects of the testicular feminization mutation (tfm) of the androgen receptor gene on BSTMPM volume and morphology in rats.
• Function of a conserved loop of the beta-domain, not involved in thiamin diphosphate binding, in catalysis and substrate activation in yeast pyruvate decarboxylase.
• Interpretation of serum C-reactive protein (CRP) levels for cardiovascular disease risk is complicated by race, pulmonary disease, body mass index, gender, and osteoarthritis.
• Leaf maximum photosynthetic rate and venation are linked by hydraulics.
• Molecular basis of acute intermittent porphyria.
• Optimising endocrine approaches for the chemoprevention of breast cancer beyond the Study of Tamoxifen and Raloxifene (STAR) trial.
• Origin and evolution of human microRNAs from transposable elements.
• Peripheral endothelin A receptor antagonism attenuates carcinoma-induced pain.
• Racial disparity in stage at diagnosis and survival among adults with oral cancer in the US.
• Randomised, placebo-controlled, double-blind study to investigate the efficacy and safety of the acute use of sodium picosulphate in patients with chronic constipation.
• Relationship of limb length inequality with radiographic knee and hip osteoarthritis.
• Role for HER2/neu and HER3 in fulvestrant-resistant breast cancer.
• SERMs: meeting the promise of multifunctional medicines.
• Spirituality and depressive symptoms in a racially diverse US sample of community-dwelling adults.
• Steroid receptors and their role in the biology and control of breast cancer growth.
• Synthesis with good enantiomeric excess of both enantiomers of alpha-ketols and acetolactates by two thiamin diphosphate-dependent decarboxylases.
• The 1',4'-iminopyrimidine tautomer of thiamin diphosphate is poised for catalysis in asymmetric active centers on enzymes.
• Tuning a potassium channel--the caress of the surroundings.
• Use of polymerase chain reaction as a diagnostic tool for neonatal sepsis can result in a decrease in use of antibiotics and total neonatal intensive care unit length of stay.
• Validity and factor structure of the AUSCAN Osteoarthritis Hand Index in a community-based sample.