Production of transforming growth factor alpha by human leukemia cells (HL-60 and U-937) during monocytic differentiation.
We have previously demonstrated that human promyelocytic HL-60 cells express transforming growth factor-alpha (TGF-alpha) during granulocytic differentiation. The present experiments were carried out in order to determine whether cells differentiated towards monocytes/macrophages will analogously express the TGF-alpha proto-oncogene product. HL-60 cells were induced to differentiate with 1 microM 1,alpha 25-dihydroxycholecalciferol (vitamin D3), and the human monocytoid cell line, U-937, was induced with 1 microM retinoic acid (RA), 0.1 microM vitamin D3, or 0.16 microM phorbol-12-myristate-13-acetate (PMA), ie experimental protocols known to induce monocyte/macrophage differentiation in these cells. In HL-60 cells, lacking constitutive TGF-alpha mRNA, vitamin D3 caused expression of the TGF-alpha gene and protein as demonstrated by Northern blot analysis and enzyme-linked immunoabsorbant assay (ELISA). In U-937 cells, showing constitutive TGF-alpha expression, RA but not vitamin D3 or PMA, caused marked increase in TGF-alpha mRNA (approximately 5-fold) and protein (approximately 3-fold) levels. In both cell lines the increase in TGF-alpha mRNA was evident within 24 h and continued throughout the observation period. Thus, it is established that differentiation of human leukemia cells towards monocytes/macrophages may be accompanied by TGF-alpha gene and protein expression in vitro. This is in conformity with the observed ability of mature activated macrophages to produce TGF-alpha.
Walz
T M
TM
Department of Cell Biology, Faculty of Health Sciences, University of Linköping, Sweden.
Malm
C
C
Nishikawa
B K
BK
Willander
K
K
Wingren
S
S
Wasteson
A
A
D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D016167:Integrin alphaXbeta2 / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D013997:Time Factors; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis*; D014212:Tretinoin / Q000494:pharmacology
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D016167:Integrin alphaXbeta2; D018950:Lipopolysaccharide Receptors; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016211:Transforming Growth Factor alpha; D014212:Tretinoin; D002117:Calcitriol