Transcriptomics

Dataset Information

12

Transcription profiling by array of human MCF7 cells overexpressing HER2 after growth with or without estrogen, tamoxifen, gefinitinib and fulvestrant


ABSTRACT: To investigate molecular mechanisms of resistance, we used two different in vivo xenograft models of estrogen receptor-positive (ER+) breast cancer, with or without HER2 over-expression (MCF7/HER2-18 and MCF7 wt, respectively). Mice with established tumors were assigned to the following treatment groups: continued estrogen supplementation (E2), estrogen deprivation (ED), ED plus tamoxifen (Tam), all with or without the EGFR tyrosine kinase inhibitor gefinitinib (G). Another group received ED plus the antiestrogen fulvestrant (MCF7 wt only). Tumors with acquired or de novo resistance to these endocrine therapies were profiled for mRNA expression using Affymetrix Genechip arrays. This SuperSeries is composed of the following subset Series:; GSE8139: Expression data from MCF7/HER2-18 xenografts; GSE8140: Expression data from MCF7 wt xenografts Experiment Overall Design: MCF7 xenografts were established in ovariectomized five to six week-old nu/nu athymic nude mice supplemented with 0.25 mg 21 day release estrogen pellets by inoculating subcutaneously (s.c.) 5E-6 cells. When tumors reached the size of 150-200 mm3 (3-5 weeks), the animals were randomly allocated to continued estrogen (E2), continued estrogen with gefitinib (E2+G; 100mg/kg, 5 days/week), estrogen withdrawal alone (ED; by removal of the estrogen pellets), and estrogen withdrawal plus tamoxifen citrate (Tam; 500 microg/animal s.c. in peanut oil, 5 days/week), with either gefitinib (Tam+G; 100mg/kg, 5 days/week) or vehicle (1% Tween 80) administered via gavage, as well as estrogen withdrawal plus fulvestrant (ICI 182,780) in the MCF7 wt model (Fulv; 5mg/mouse s.c. once weekly), and estrogen withdrawal with gefitinib (ED+G). Tumors were harvested for molecular studies when they became resistant to treatment and reached the size of 1000 mm3 (n=7). Experiment Overall Design: Refer to individual Series

ORGANISM(S): Homo sapiens  

SUBMITTER: Chad Creighton  

PROVIDER: E-GEOD-8141 | ArrayExpress | 2008-12-05

SECONDARY ACCESSION(S): GSE8141PRJNA101027

REPOSITORIES: GEO, ArrayExpress

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Publications

Development of resistance to targeted therapies transforms the clinically associated molecular profile subtype of breast tumor xenografts.

Creighton Chad J CJ   Massarweh Suleiman S   Huang Shixia S   Tsimelzon Anna A   Hilsenbeck Susan G SG   Osborne C Kent CK   Shou Jiang J   Malorni Luca L   Schiff Rachel R  

Cancer research 20080901 18


The effectiveness of therapies targeting specific pathways in breast cancer, such as the estrogen receptor or HER2, is limited because many tumors manifest resistance, either de novo or acquired, during the course of treatment. To investigate molecular mechanisms of resistance, we used two xenograft models of estrogen receptor-positive (ER+) breast cancer, one with and one without HER2 overexpression (MCF7/HER2-18 and MCF7 wt, respectively). Mice with established tumors were assigned to the foll  ...[more]

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