Involvement of transforming growth factor-α and its receptor in a model of DES-induced renal carcinogenesis in the Syrian hamster.

Autor: Wattiez, Ruddy, Nonclercq, Denis, Journé, Fabrice, Toubeau, Gérard, Zanen, Jacqueline, Falmagne, Paul, Heuson-Stiennon, Jeanine-Anne
Zdroj: Carcinogenesis; 1996, Vol. 17 Issue 8, p1615-1622, 8p
Abstrakt: This study explores the role played by TGFα in estrogen-induced renal tumors. Tumors were induced in male Syrian hamster by chronic administration of diethylstilbestrol (DES). Six experimental groups (n = 5–9) were chronically exposed to DES and sacrificed after 1, 2, 4, 6, 9 and 11 months, respectively. In the course of treatment, the nephrons were the site of an important increase of cell turnover, which was characterized by a process of hyperplasia/dysplasia in proximal tubules preceding the neoplastic transformation. In treated animals and in controls, the analysis of renal tissue by Western blot revealed the presence of a 6 kDa polypeptide crossreacting with anti-TGFα antibody. In controls, TGFα immunoreactivity was localized in proximal and in distal tubules. Before tumor development (1–4 months), TGFα RIA showed an increase of TGFα concentration in renal tissue, in parallel with the increased cell proliferation observed in proximal tubules. In addition, Western blot analysis also demonstrated in kidney tissue the presence of a 165 kDa protein displaying the immunoreactivity of EGF/TGFα receptor. The receptor immunoreactivity was localized in proximal tubular cells suggesting an involvement of TGFα in tubular epithelial growth through autocrine or paracrine pathways. In large neoplasms, immunocytochemistry revealed only clusters of transformed cells intensely stained by the anti-TGFα antibody. These cells displayed the appearance of stellate or polyhedric cells infiltrating adjacent neoplastic tissues. Antisera raised against intra-or extracytoplasmic domains of the EGF/TGFα receptor were assayed to localize this receptor in the tumors. In contrast with tubular structures, immunoreactivity to EGF/TGFα receptor was never detected in tumoral tissue. The apparent absence of EGF/TGFα receptor immunoreactivity in malignant cells seems to exclude an involvement of this growth factor in the tumorigenic process, although it could be involved in tumor neovascularization. [ABSTRACT FROM PUBLISHER]
Databáze: Complementary Index