Expression of the c-ErbB-2/HER2 proto-oncogene in normal hematopoietic cells.
The HER2/c-ErbB-2 proto-oncogene is overexpressed in 25-30% of human breast cancers. We previously reported the c-ErbB-2 transcript in mononuclear cells (MNC) from bone marrow (BM), peripheral blood (PB), and mobilized PB (MPB). Here, we describe extensively the expression pattern of c-ErbB-2 mRNA and protein in normal adult hematopoietic tissue and cord blood (CB)-derived cells. Quantitative reverse transcriptase-polymerase chain reaction shows that the c-ErbB-2 transcript is expressed in hematopoietic cells at low levels if compared with normal epithelial and breast cancer cells. The c-ErbB-2 protein was detected predominantly in MNC from PB and CB by Western blot analysis. Flow cytometry revealed that CD15+, CD14+, and glycophorin A+ subpopulations express c-ErbB-2 protein, whereas lymphocytes are c-ErbB-2-negative. The c-ErbB-2 expression is higher in CB MNC. More than 90% of BM- and MPB-derived CD34+ progenitors are c-ErbB-2-negative; by contrast, 5-40% of CB-derived CD34+ progenitors express c-ErbB-2. We found that c-ErbB-2 protein is up-regulated during cell-cycle recruitment of progenitor cells. Similarly, it increases in mature, hematopoietic proliferating cells. This study reports the first evidence that the c-ErbB-2 receptor is correlated to the proliferating state of hematopoietic cells. Studies in progress aim to clarify the role of c-ErbB-2 in regulation of this process in hematopoietic tissues.
Leone
Francesco
F
Department of Oncological Sciences, University of Torino Medical School, Institute for Cancer Research and Treatment, IRCC Candiolo, Italy. francesco.leone@ircc.it
Perissinotto
Eliana
E
Cavalloni
Giuliana
G
Fonsato
Valentina
V
Bruno
Stefania
S
Surrenti
Nadia
N
Hong
Dengli
D
Capaldi
Antonio
A
Geuna
Massimo
M
Piacibello
Wanda
W
Aglietta
Massimo
M
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D002455:Cell Division; D002478:Cells, Cultured; D005312:Fetal Blood / Q000737:chemistry / Q000166:cytology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000737:chemistry; D006413:Hematopoietic System / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C000715470:MAS1 protein, human