RanBPM interacts with psoriasin in vitro and their expression correlates with specific clinical features in vivo in breast cancer

BMC Cancer. 2002 Nov 6;2:28. doi: 10.1186/1471-2407-2-28.

Abstract

Background: Psoriasin has been identified as a gene that is highly expressed in pre-invasive breast cancer, but is often downregulated with breast cancer progression. It is currently unknown whether psoriasin influences epithelial cell malignancy directly or by affecting the surrounding environment. However the protein is found in the nucleus, cytoplasm as well as extracellularly. In the present study we have sought to identify potential psoriasin-binding proteins and to describe their expression profile in breast tumors.

Methods: The yeast two-hybrid method was used to identify potential binding partners for psoriasin. The interaction of psoriasin with RanBPM was confirmed in-vitro by co-immunoprecipitation. The expression of RanBPM and psoriasin was measured by RT-PCR in a series of breast cell lines, breast tumors and primary lymphocytes.

Results: We have identified RanBPM as an interacting protein by the yeast two-hybrid assay and confirmed this interaction in-vitro by co-immunoprecipitation. RT-PCR analysis of RanBPM mRNA expression in cell lines (n = 13) shows that RanBPM is widely expressed in different cell types and that expression is higher in tumor than in normal breast epithelial cell lines. RanBPM expression can also be induced in peripheral blood mononuclear cells by treatment with PHA. RanBPM mRNA is also frequently expressed in invasive breast carcinomas (n = 64) and a higher psoriasin/RanBPM ratio is associated with both ER negative (p < 0.0001) and PR negative status (p < 0.001), and inflammatory cell infiltrates (p < 0.0001) within the tumor.

Conclusions: These findings support the hypothesis that psoriasin may interact with RanBPM and this may influence both epithelial and stromal cells and thus contribute to breast tumor progression.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Cell Line
  • Cytoskeletal Proteins
  • Female
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • S100 Calcium Binding Protein A7
  • S100 Proteins
  • Saccharomyces cerevisiae / genetics
  • Tumor Cells, Cultured
  • Two-Hybrid System Techniques
  • ran GTP-Binding Protein / genetics
  • ran GTP-Binding Protein / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Calcium-Binding Proteins
  • Cytoskeletal Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • Ran binding protein 9
  • S100 Calcium Binding Protein A7
  • S100 Proteins
  • S100A7 protein, human
  • ran GTP-Binding Protein