Transcriptomics

Dataset Information

38

Estrogen insensitivity in a model of estrogen receptor positive breast cancer lymph node metastasis.


ABSTRACT: The lymphatic system is a common avenue for the spread of breast cancer cells and dissemination through it occurs at least as frequently as hematogenous metastasis. Approximately 75% of primary breast cancers are estrogen receptor (ER) positive and the majority of these maintain receptor expression as lymph node (LN) metastases. However, it is unknown if ER function is equivalent in cancer cells growing in the breast and in the LNs. We have developed a model to assess estrogen responsiveness in ER(+) breast tumors and LN metastases. Fluorescent ER(+) MCF-7 tumors were grown in ovariectomized nude mice supplemented with estradiol. Once axillary LN metastasis arose, estradiol was withdrawn (EWD), for 1 or 4 weeks, or continued, to assess estradiol responsiveness. On EWD, proliferation rates fell similarly in tumors and LN metastases. However, estradiol-dependent ER down-regulation and progesterone receptor induction were deficient in LN metastases, indicating that ER-dependent transcriptional function was altered in the LN. Cancer cells from estradiol-treated and EWD primary tumors and matched LN metastases were isolated by laser capture microdissection. Global gene expression profiling identified transcripts that were regulated by the tissue microenvironment, by hormones, or by both. Interestingly, numerous genes that were estradiol regulated in tumors lost estradiol sensitivity or were regulated in the opposite direction by estradiol in LN metastases. We propose that the LN microenvironment alters estradiol signaling and may contribute to local antiestrogen resistance. Keywords: Breast cancer lymph node metastasis, ER positive, MCF7, xenograft Overall design: 10 samples, including 3 each of estrogen and estrogen withdrawn axillary lymph nodes and 2 each of estrogen and estrogen withdrawn primary mammary gland tumors.

INSTRUMENT(S): [U133_X3P] Affymetrix Human X3P Array

ORGANISM(S): Mus musculus  

SUBMITTER: Wendy Dye 

PROVIDER: GSE11317 | GEO | 2008-05-02

SECONDARY ACCESSION(S): PRJNA106629

REPOSITORIES: GEO

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