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Inflammatory Genes Differentially Regulated in ER-negative Breast Cancer

Inflammatory genes from KEGG cytokine-chomokine pathways in the GSE5460 dataset (n=129 breast tumor samples) were analyzed by a univariate test (p<0.001) and hierarchically clustered.

While breast cancer remains the leading cause of cancer-related death in women, substantial progress has been made in therapies targeting estrogen receptor (ER)-positive cancer (e.g., selective estrogen receptor modulators, or SERMs) as well as in therapies targeting the overexpression of human epidermal growth factor receptor 2 (HER2).  The overexpression of HER2 and activation of hormone-related signaling are major initiating mechanisms responsible for the development and maintenance of both HER2-positive and ER-positive progesterone receptor (PR)-positive breast cancers. However, the pathways underlying the development and maintenance of ER-negative, PR-negative, HER2-negative cancer, also known as triple-negative or basal-like cancer, are unknown. Using in vitro genomic and expression profiling strategies1 in patient biopsies and basal-like breast cancer cells, we have discovered a subset of inflammatory cytokines and chemokines highly expressed and enriched in ER-negative and triple-negative tumors.  While some of these genes have been shown to play pivotal roles in other types of cancer, the significance of this cytokine/chemokine signature in human basal-like breast tumors remains unclear.  Our investigation of this pathway could provide critical understanding of the mechanisms underlying the progression of certain subtypes of basal-like cancer.  If the mechanisms that initiate these tumors and facilitate their growth, or conversely, those that prevent or hinder their inception, development and metastasis, could be defined, they could provide useful targets, diagnostics, and approaches for preventing and treating triple-negative breast cancer as well as other types of cancer with similar molecular and genetic profiles.

References:

  1. Speers C, Tsimelzon A, Sexton K, Herrick AM, Gutierrez C, Culhane A, Quackenbush J, Hilsenbeck S, Chang J and Brown P. Identification of novel kinase targets for the treatment of estrogen receptor-negative breast cancer. Clinical Cancer Research 15(20): 6327-40, 2009.

Lab members working on this project:  

Zachary Hartman, Ph.D., Jamal Hill, Senior Research Assistant and Yun Zhang, Senior Research Assistant.


© 2014 The University of Texas MD Anderson Cancer Center