title: BIGH3 is overexpressed in clear cell renal cell carcinoma.
abstract: To identify new target marker genes in renal cell carcinoma (RCC), we compared the gene expression profiles of clear cell RCC (cc-RCC) and normal kidney tissue using serial analysis of gene expression. Our results revealed that the transforming growth factor beta induced 68 kDa protein (TGF-betaI: beta ig-h3 (BIGH3), plasminogen activator inhibitor-1 (PAI-1) and transforming growth factor beta1 (TGF-beta1) genes are up-regulated in cc-RCC. To further assess the role of BIGH3 in RCC, we investigated the mRNA expression levels of BIGH3, TGFbeta1, PAI-1 and also of TGF-beta1 related genes in 53 RCC and 30 normal kidney tissues by quantitative real-time RT-PCR (QRT-PCR). We further determined the BIGH3 protein levels in 52 cc-RCC paraffin-embedded tissue samples by immunohistochemistry. BIGH3 mRNA was found to be highly overexpressed in cc-RCC compared with normal tissues with an average ratio of 27. The mRNA levels of TGF-beta1 and PAI-1 were also detected at significantly elevated levels in these cancers. Immunohistochemical analysis of BIGH3 also revealed strong staining in the majority of the cc-RCC samples. In addition, the up-regulation of BIGH3 and PAI-1 was found to correlate with the clinicopathological parameters associated with a poorer patient outcome, whereas TGF-beta1 expression was determined to be unrelated to cancer progression. Strong BIGH3 staining thus tended to be associated with a poor prognosis. BIGH3 was also induced in some RCC cell lines by TGF-beta1 stimulation and this correlated well with PAI-1 up-regulation, suggesting that these enhancements are regulated by a similar mechanism in these tumors.
authors: Department of Urology, National Defense Medical College, Saitama 359-8513, Japan.
authors: Masanori
authors: M
authors: Yamanaka
authors: Fumihiro
authors: F
authors: Kimura
authors: Yutaka
authors: Y
authors: Kagata
authors: Nobuo
authors: N
authors: Kondoh
authors: Tomohiko
authors: T
authors: Asano
authors: Mikio
authors: M
authors: Yamamoto
authors: Masamichi
authors: M
authors: Hayakawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000032:analysis / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000494:pharmacology; D000099222:betaIG-H3 Protein
chemical_list: D016326:Extracellular Matrix Proteins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000099222:betaIG-H3 Protein