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

Abstract

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.

• Authors: Triantafyllia Koletsa, Ioannis Kostopoulos, Elpida Charalambous, Barbara Christoforidou, Eleni Nenopoulou, Vassiliki Kotoula
• Journal: Neoplasia (New York, N.Y.) (Neoplasia) Vol. 10 Issue 7 Pg. 687-96 (Jul 2008) ISSN: 1476-5586 [Electronic] United States
• PMID: 18592003 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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