Expression of the c-ErbB-2/HER2 proto-oncogene in normal hematopoietic cells

Abstract

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.

Neuregulin1-induced cell migration is impaired in schizophrenia: association with neuregulin1 and catechol-o-methyltransferase gene polymorphisms

“…In this study, we examined NRG1-ErbB signaling in patients with schizophrenia using EBVtransformed B lymphoblasts because they are easily established from patients and can be maintained to investigate various cellular and molecular biological functions. Previous studies have confirmed the expression of ErbB receptors in primary hematopoietic cells, 46 B cell leukemia-derived lymphoblasts 47,48 and multiple myeloma cells, 49 suggesting that hematopoietic cells, especially the B-cell lineage, express ErbB receptors. Consistent with these previous findings, we found that ErbB2 and ErbB3 transcripts and proteins were expressed in all the EBV-transformed B lymphoblasts tested.…”

The α2β1 integrin is a metastasis suppressor in mouse models and human cancer

“…Figure 3C shows the ratio of circulating Neu-expressing cells relative to GAPDH in the blood at the time of sacrifice when the primary tumors in the WT/Neu and α 2 -null/Neu mice were of similar size; α 2 -null/Neu mice had a significantly larger proportion of these cells than WT/Neu mice (P = 0.005). Since c-ErbB2/Her2 is expressed in normal hematopoietic cells, the number of circulating tumor cells was also characterized by qRT-PCR for cytokeratin 19 (28). As shown in Supplemental Figure 3, increased numbers of circulating, cytokeratin 19-expressing cells were identified in the peripheral blood of tumor-bearing, α 2 -null/Neu in comparison with WT/Neu mice at the time of sacrifice.…”

The cell surface glycoprotein CDCP1 in cancer—Insights, opportunities, and challenges

“…These proteins include epidermal growth factor receptors targeted in colon, lung, and head and neck cancers and the human epidermal growth factor receptor-2 (HER-2) in breast and other cancers (21). Of relevance, HER-2 has been detected in skin, breast, and placenta as well as in epithelial cells of the gastrointestinal, respiratory, reproductive, and urinary tracts (22) and has been detected on subsets of hematopoietic cells (23) and also functions in muscle (24).…”