Altered Expression of Transforming Growth Factor-beta1 and Its Receptors in Renal Cell Carcinoma

Kang, Sang Soo; Min, Kyung Dai; Jung, Seung Il; Kim, Sae Yeon; Oh, Bong Ryoul; Ryu, Soo Bang; Park, Yang Il

Abstract

PURPOSE
Resistance to the potent growth inhibitory effects of transforming growth factor-beta (TGF-beta) is a characteristic of many malignancies. TGF-beta insensitivity has been attributed to alterations in the number and function of the TGF-beta receptors as well as disturbances of downstream signal transduction. Paradoxically, increased levels of TGF-beta1 have been demonstrated in several types of malignant tumors. To determine what role of TGF-beta1 and its receptors may have in renal cell carcinoma (RCC), we examined their expression in RCC and adjacent normal kidney tissues.
MATERIALS AND METHODS
Fifty-six surgically resected tumor specimens of RCC and non-tumor specimens of kidney were analyzed for the mRNA expression of TGF-beta1 by quantitative reverse transcription polymerase chain reaction (RT-PCR) and three TGF-beta receptors (RI, RII, and RIII) by RT-PCR. Immunohistochemical analysis was performed to localize their expressions.
RESULTS
All the fifty six non-tumor specimens of kidney showed expression of TGF-beta1, RI, RII, and RIII. All of tumor specimens demonstrated expression of TGF-beta1. Compared with non-tumor kidney specimens, primary renal cell carcinoma demonstrated significant overexpression (4- to 7-fold increase) of the TGF-beta1 mRNA transcripts (P<0.001). Loss of mRNA expression of RI, RII, RIII were observed in 8 (14.3%), 15 (26.8%), and 18 of 56 (32.1%) tumor specimens, respectively. There were significant associations between loss of RII, RIII gene expression and histologic grade (P<0.001 and P<0.01, respectively), and between tumor stage (P<0.01 and P<0.05, respectively). Immunohistochemical analysis demonstrated that TGF-beta1 and its receptors were localized to tumor cytoplasm, and their intensity reflected the mRNA expression in these tissues.
CONCLUSIONS
Altered expression of TGF-beta1 and its receptors consistently were remarkable in renal cell carcinoma compared with non-tumor specimens of kidney. These data suggest that enhanced expression of TGF-beta1 as well as the loss of expression of RI, RII, and RIII contribute to carcino-genesis of kidney and tumor progression.