A splice variant of HER2 corresponding to Herstatin is expressed in the noncancerous breast and in breast carcinomas.
| Τίτλος | A splice variant of HER2 corresponding to Herstatin is expressed in the noncancerous breast and in breast carcinomas. |
| Publication Type | Journal Article |
| Year of Publication | 2008 |
| Authors | Koletsa, T., Kostopoulos I., Charalambous E., Christoforidou B., Nenopoulou E., & Kotoula V. |
| Journal | Neoplasia |
| Volume | 10 |
| Issue | 7 |
| Pagination | 687-96 |
| Date Published | 2008 Jul |
| ISSN | 1476-5586 |
| Λέξεις κλειδιά | Adult, Aged, Aged, 80 and over, Alternative Splicing, Base Sequence, Breast Neoplasms, Carcinoma, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genes, erbB-2, Humans, Intercellular Signaling Peptides and Proteins, Mammary Glands, Human, Middle Aged, Oligonucleotide Array Sequence Analysis, Paracrine Communication, Protein Isoforms, RNA, Messenger |
| 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. |
| DOI | 10.1593/neo.08314 |
| Alternate Journal | Neoplasia |
| PubMed ID | 18592003 |
| PubMed Central ID | PMC2434206 |
