Altered expression of members of the IGF-axis in clear cell renal cell carcinoma.
Renal cell carcinoma (RCC) is a heterogeneous disease and its biology is poorly understood. The commonest subtype identified is clear cell RCC. The insulin-like growth factor axis is intimately involved with many cellular roles including that of renal development. Dysregulation of this axis has frequently been demonstrated in cancer. In this study, we examine the expression of several IGF-axis components, including receptors, ligands, and binding proteins in clear cell renal cell carcinoma. A series of clear cell RCCs with matched normal kidney from the same individuals were obtained. Total RNA was extracted and expression levels of genes examined using RNase protection analysis. We confirm the dysregulation of the IGF-axis within clear cell renal cell carcinoma including the upregulation of IGFBP-3, which is further validated by immunohistochemical staining on a tissue array containing 50 RCC: positive staining in 29/30 clear cell; 1/10 papillary and 0/10 chromophobe. In addition, we demonstrate that the expression of the A isoform of the insulin receptor is significantly upregulated, while that of IGFBP-5 are significantly downregulated in this tumour subtype.
Takahashi
Masayuki
M
Laboratory of Cancer Genetics, Van Andel Research Institute, 333 Bostwick NE, Grand Rapids, MI 49503, USA.
Papavero
Veronica
V
Yuhas
Jason
J
Kort
Eric
E
Kanayama
Hiro-Omi
HO
Kagawa
Susumu
S
Baxter
Robert C
RC
Yang
Ximing J
XJ
Gray
Steven G
SG
Teh
Bin Tean
BT
D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000096:biosynthesis; D008297:Male; D012313:RNA / Q000096:biosynthesis; D011972:Receptor, Insulin / Q000096:biosynthesis; D012260:Ribonucleases / Q000494:pharmacology; D013002:Somatomedins / Q000096:biosynthesis*; D015854:Up-Regulation
D018972:Insulin-Like Growth Factor Binding Protein 3; D018975:Insulin-Like Growth Factor Binding Protein 5; D013002:Somatomedins; D012313:RNA; D011972:Receptor, Insulin; D012260:Ribonucleases