A mouse mammary gland involution mRNA signature identifies biological pathways potentially associated with breast cancer metastasis

J Mammary Gland Biol Neoplasia. 2009 Jun;14(2):99-116. doi: 10.1007/s10911-009-9120-1. Epub 2009 Apr 30.


Mouse mammary gland involution resembles a wound healing response with suppressed inflammation. Wound healing and inflammation are also associated with tumour development, and a 'wound-healing' gene expression signature can predict metastasis formation and survival. Recent studies have shown that an involuting mammary gland stroma can promote metastasis. It could therefore be hypothesised that gene expression signatures from an involuting mouse mammary gland may provide new insights into the physiological pathways that promote breast cancer progression. Indeed, using the HOPACH clustering method, the human orthologues of genes that were differentially regulated at day 3 of mammary gland involution and showed prolonged expression throughout the first 4 days of involution distinguished breast cancers in the NKI 295 breast cancer dataset with low and high metastatic activity. Most strikingly, genes associated with copper ion homeostasis and with HIF-1 promoter binding sites were the most over-represented, linking this signature to hypoxia. Further, six out of the ten mRNAs with strongest up-regulation in cancers with poor survival code for secreted factors, identifying potential candidates that may be involved in stromal/matrix-enhanced metastasis formation/breast cancer development. This method therefore identified biological processes that occur during mammary gland involution, which may be critical in promoting breast cancer metastasis that could form a basis for future investigation, and supports a role for copper in breast cancer development.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Breast / metabolism
  • Breast / pathology
  • Breast / physiology*
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Transformation, Neoplastic / genetics
  • Ceruloplasmin / genetics
  • Ceruloplasmin / physiology
  • Cluster Analysis
  • Copper / metabolism
  • Cytoskeletal Proteins / genetics
  • Extracellular Matrix / metabolism
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic
  • Homeostasis
  • Humans
  • Insulin-Like Growth Factor Binding Protein 5 / genetics
  • Insulin-Like Growth Factor Binding Protein 5 / metabolism
  • Lactation / genetics*
  • Mammary Glands, Animal / metabolism
  • Mammary Glands, Animal / pathology
  • Mammary Glands, Animal / physiology*
  • Mammary Neoplasms, Experimental / genetics*
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Neoplasm Metastasis / genetics*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • RNA, Messenger / analysis*
  • RNA, Messenger / genetics
  • Stromal Cells / metabolism


  • Cytoskeletal Proteins
  • Insulin-Like Growth Factor Binding Protein 5
  • Neoplasm Proteins
  • RNA, Messenger
  • Copper
  • Ceruloplasmin