A splice variant of HER2 corresponding to Herstatin is expressed in the noncancerous breast and in breast carcinomas

Neoplasia. 2008 Jul;10(7):687-96. doi: 10.1593/neo.08314.


Herstatin (HST) is an alternatively spliced HER2 product with growth-inhibitory properties in experimental cancer systems. The role of HST in adult human tissues and disease remains unexplored. Here, we investigated HST expression at the mRNA and protein (immunohistochemistry [IHC]) level in parallel with parameters reflecting HER activation in 187 breast carcinomas and matched noncancerous breast tissues (NCBT). Noncancerous breast tissues demonstrated the highest HST/HER2 transcript ratios corresponding to a few positive epithelial and stromal cells by IHC. Although HST/HER2 transcript ratios in tumors were inversely associated with HER2 IHC grading (P = .0048 for HER2 IHC-1+ and P = .0006 for HER2 IHC-2+ vs HER2-negative tumors), relative HST expression within the same tumor/NCBT system remained constant. HST/HER2 ratios did not predict the presence of HST protein, which was found in 46 (25%) of 187 tumors. A subgroup of HER2 IHC-3+ tumors exhibited high HST/HER2 transcript ratios, strong HST protein positivity, and cytoplasmic phospho-Akt/PKB and p21(CIP1/WAF1) localization. In conclusion, HST may act as a paracrine factor in the adult breast. Because HST is described as an endogenous pan-HER inhibitor, the presence of this protein in breast carcinomas may portent the inefficiency of exogenous efforts to block HER2 dimerization, whereas its absence may justify such interventions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alternative Splicing / genetics
  • Base Sequence
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genes, erbB-2*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Mammary Glands, Human / metabolism*
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Paracrine Communication / genetics
  • Protein Isoforms / genetics
  • RNA, Messenger / metabolism


  • Intercellular Signaling Peptides and Proteins
  • Protein Isoforms
  • RNA, Messenger
  • herstatin