title: In vivo evidence of htid suppressive activity on ErbB-2 in breast cancers over expressing the receptor.
abstract: BACKGROUND
  Htid encoded proteins are physiological partners of a wide spectrum of molecules relevant to neoplastic transformation. One of the molecular ligands of the cytosolic hTid-L and hTid-I forms is the ErbB-2 receptor variably over expressed in diverse solid tumors. Altered ErbB-2 signalling is associated with an unfavourable prognosis in about 30% of human breast malignancies.
  
  
  METHODS
  We evaluated htid and HER-2 expression by quantitative real time PCR in tumors of different TNMG status and by immunohistochemistry in a cohort of breast tumors of the Luminal A, B, HER-2 and triple negative subtype.
  
  
  RESULTS
  The RT-PCR analysis revealed that aberrant expression of all three htid forms correlates with malignant transformation. Furthermore, elevated hTid-L expression can be associated with less aggressive tumors. The immunohistochemical testing revealed that tumors of the luminal A subtype are characterized by a high level of htid (81%). In contrast htid expression is significantly lower in tumors of the Luminal B (20%) and HER-2 (18%) subtype over expressing the receptor and in the triple negative (40%) more aggressive malignancies. A statistically significant inverse correlation between htid and ErbB-2 expression was found in human breast (p < 0,0001) and non-mammary tumors (p < 0,007), and in transgenic mice carrying the rat HER-2/neu oncogene.
  
  
  CONCLUSIONS
  Our findings provide in vivo evidence that htid is a tissue independent and evolutionarily conserved suppressor of ErbB-2.
authors.affiliation: Institute of Medical Microbiology and Hygiene, Comparative Tumor Biology Group, University Medical Center, Johannes Gutenberg University, Obere Zahlbacher Str 63, 55131 Mainz, Germany. kurzik@uni-mainz.de
authors.forename: Ursula
authors.initials: U
authors.lastname: Kurzik-Dumke
authors.forename: Manuela
authors.initials: M
authors.lastname: Hörner
authors.forename: Maria R
authors.initials: MR
authors.lastname: Nicotra
authors.forename: Michael
authors.initials: M
authors.lastname: Koslowski
authors.forename: Pier G
authors.initials: PG
authors.lastname: Natali
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D042361:Mammary Glands, Human / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D050956:HSP40 Heat-Shock Proteins; D008024:Ligands; D018719:Erb-b2 Receptor Tyrosine Kinases; C120664:DNAJA3 protein, human