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 ß induced 68 kDa protein (TGF-ßI: ß ig-h3 (BIGH3), plasminogen activator inhibitor-1 (PAI-1) and transforming growth factor ß1 (TGF-ß1) genes are upregulated in cc-RCC. To further assess the role of BIGH3 in RCC, we investigated the mRNA expression levels of BIGH3, TGFß1, PAI-1 and also of TGF-ß1 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-ß1 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-ß1 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-ß1 stimulation and this correlated well with PAI-1 upregulation, suggesting that these enhancements are regulated by a similar mechanism in these tumors.

Targeted Disruption of TGFBI in Mice Reveals Its Role in Regulating Bone Mass and Bone Size through Periosteal Bone Formation

“…We speculate that TGFBI may have a dual role, promoting the proliferation of osteoblast and chondrocyte precursors and inhibiting the differentiation of mature osteoblasts, with the net result of increasing bone mass and bone size. Previous findings in other studies support a role of TGFBI in cell proliferation: TGFBI is highly expressed in the growth area and cancer cells and involved in tumor invasion and metastasis [13,25,26]. A gene-expression analysis also indicated the biphasic nature of TGFBI in the fact that the mRNA and protein of TGFBI were highly expressed in the early stages of chondrocyte differentiation but decreased in the later stages [47].…”

“…Although it is present in a wide range of tissues, TGFBI is highly expressed in bone, cartilage, cornea, kidney, and skin [8,21]. It is an important molecule studied for cancers [8,[22][23][24][25][26][27][28][29][30], corneal dystrophies [8,31,32], and wound healing [15,[33][34][35]. A few in vitro studies related to bone metabolism have found that TGFBI has a positive effect on the adhesion and migration of osteoblasts and a negative effect on the differentiation and mineralization of osteoblasts as well as hypertrophic chondrocytes [17,18,36,37].…”

Identification and validation of TGFBI as a promising prognosis marker of clear cell renal cell carcinoma

“…The cancer microarray database ONCOMINE [24] revealed other microarray gene-expression studies in which TGFBI was also reported as one of the most significant genes upregulated in RCC tumors, when compared with adjacent normal kidney tissue. Recently, it has been shown that there was an association between TGFBI expression and the von Hippel Lindau (VHL) [25]. TGFBI is important for the adhesion, the migration, and the invading ability of RCC cells especially for cell lines with inactive VHL [23].…”

Novel Gefitinib Formulation with Improved Oral Bioavailability in Treatment of A431 Skin Carcinoma

“…Over expression of Poly [ADP-ribose] polymerase 1 was found to be significantly down regulated in Gef-SD groups (46). BIGH3 promotes adhesion and invasion potential of cancer cells (47) and its expression was also significantly down regulated in Gef-SD treated animals.…”