Identification and expression analysis of an N-terminally truncated isoform of human PDGF-C.
Platelet-derived growth factor C (PDGF-C) is a member of the PDGF family that plays an important role in developmental and physiological processes, and in human diseases. Here, we report a novel splice variant of human PDGF-C (PDGF-Cb), which encodes an N-terminally truncated protein, lacking the signal peptide and CUB domain. This variant is coexpressed with PDGF-C in all normal tissues analyzed. PDGF-Cb is produced as a cytoplasmic protein, and has a similar intracellular localization to PDGF-C, but is not secreted from transfected cells. Further, we show that PDGF-Cb can form heterodimers (PDGF-CCb) with PDGF-C, which is thereby retained and degraded within cells. In primary renal cell carcinoma (RCC), expression of the two alternatively spliced transcripts was different. Generally, expression of the full-length PDGF-C transcript was increased in RCC tumors, whereas expression of PDGF-Cb was not in the 30 analyzed cases with paired RCC tumor tissues and normal renal tissues. Based on these findings, we suggest that PDGF-Cb might act as a dominant negative molecule regulating the secretion of PDGF-C, and that deregulation of full-length PDGF-C is involved in RCC tumorigenesis.
Zhao
Jian
J
Department of Oncology-Pathology, Karolinska Institutet, CCK R8:05, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. Jian.Zhao@ki.se
Liu
Zhaoxu
Z
Liu
Tong
T
Nilsson
Sten
S
Nistér
Monica
M
D000328:Adult; D000368:Aged; D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002292:Carcinoma, Renal Cell / Q000235:genetics; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D017124:Conserved Sequence; D019281:Dimerization; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics; D008222:Lymphokines / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008322:Mammals; D008875:Middle Aged; D008969:Molecular Sequence Data; D010982:Platelet-Derived Growth Factor / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D020033:Protein Isoforms; D012333:RNA, Messenger; D011994:Recombinant Proteins; C411423:platelet-derived growth factor C