Expression of messenger RNAs for platelet-derived growth factor and transforming growth factor-alpha and their receptors in human malignant glioma cell lines.
Formal proof for an involvement of autocrine stimulation in the disturbed growth of malignant cells has been difficult to obtain, in part due to lack of precise methods of assessing growth factor production and receptor occurrence. In this study we have analyzed the mRNA levels for two growth factors and the corresponding receptors in a number of established human malignant glioma cell lines. Twenty-one tested lines all contained transcripts for the platelet-derived growth factor (PDGF) A chain while 16-17 of 21 expressed the c-sis/PDGF B chain gene; these two genes were expressed independently of each other. PDGF receptor transcripts were present in 15-16 of the 21 lines. Transcripts for the epidermal growth factor receptor were found in all 15 tested lines, in 2 of them at high levels, and the corresponding ligand transforming growth factor-alpha was found in 11 of 15 lines. No amplification or structural rearrangements of the genes, as analyzed by Southern blot hybridization, could explain the varying expression of PDGF A and B chain transcripts or the elevated levels of epidermal growth factor receptor mRNA. A correlation was found between cell morphology and expression of growth factor and receptor mRNA in these lines. The highest amount of PDGF receptor transcripts was found in cells with fibroblast-like morphology, and c-sis/B chain transcripts were found in small cell types and in cells with astrocyte-like morphology, while no clear relationship was found between PDGF receptor and A chain transcript levels or between morphology and A chain transcripts. It is possible that the findings reflect a coordinated expression of these genes in the progenitor cells. In conclusion, the data imply the existence of two possible autocrine loops in human malignant glioma lines, affecting the PDGF and epidermal growth factor receptor pathways.
Nistér
M
M
Department of Pathology, University of Uppsala, University Hospital, Sweden.
Libermann
T A
TA
Betsholtz
C
C
Pettersson
M
M
Claesson-Welsh
L
L
Heldin
C H
CH
Schlessinger
J
J
Westermark
B
B
D002460:Cell Line; D004247:DNA / Q000032:analysis; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005910:Glioma / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D010455:Peptides / Q000235:genetics*; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D011061:Poly A / Q000032:analysis; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics*; D017479:Receptors, Platelet-Derived Growth Factor; D015291:Transforming Growth Factors
D010455:Peptides; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011061:Poly A; D004815:Epidermal Growth Factor; D012313:RNA; D015291:Transforming Growth Factors; D004247:DNA; D066246:ErbB Receptors; D017479:Receptors, Platelet-Derived Growth Factor