Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human tamoxifen-resistant MCF-7 wild-type murine xenograft tumors with E2-supplemented tumors MCF7 xenografts


ABSTRACT: In order to help determine the genes involved in resistance of breast cancer to endocrine therapy, we compared global gene expression profiles of tamoxifen-resistant MCF-7 WT xenograft tumors with E2-supplemented tumors. 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) and estrogen withdrawal plus tamoxifen citrate. Tumors were harvested for molecular studies when they became resistant to treatment and reached the size of 1000 mm3 (n=7).

ORGANISM(S): Homo sapiens

SUBMITTER: Chad Creighton 

PROVIDER: E-GEOD-7327 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Tamoxifen resistance in breast tumors is driven by growth factor receptor signaling with repression of classic estrogen receptor genomic function.

Massarweh Suleiman S   Osborne C Kent CK   Creighton Chad J CJ   Qin Lanfang L   Tsimelzon Anna A   Huang Shixia S   Weiss Heidi H   Rimawi Mothaffar M   Schiff Rachel R  

Cancer research 20080201 3


Not all breast cancers respond to tamoxifen, and many develop resistance despite initial benefit. We used an in vivo model of estrogen receptor (ER)-positive breast cancer (MCF-7 xenografts) to investigate mechanisms of this resistance and develop strategies to circumvent it. Epidermal growth factor receptor (EGFR) and HER2, which were barely detected in control estrogen-treated tumors, increased slightly with tamoxifen and were markedly increased when tumors became resistant. Gefitinib, which i  ...[more]

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