TGF beta1, a multifunctional growth modulator, inhibits the proliferation o
f epithelial eels. TGF beta1 signaling is dependent on the heterodimerizati
on of the TGF beta1 receptor II (TGF beta 1RII) with the TGF beta1 receptor
I (TGF beta 1RI). The cytoplasmic proteins Smads are the mediators of the
TGF beta1 signal. TGF beta1 regulates adult and fetal adrenal growth and fu
nction. Previously we have shown by Northern analysis that TGF beta 1mRNA w
as well expressed in normal adrenal and in adrenocortical adenomas but redu
ced in carcinomas. To investigate whether TGF beta1 receptors may act as tu
mor suppressors of adrenal tumorigenesis, 16 adenomas and 12 carcinomas wer
e studied. We have used SSCP analysis to scan for inactivating mutations in
carcinomas. All tumor samples were negative for somatic alterations of bot
h genes. A competitive RT-PCR system was developed to compare the levels of
expression of TGF beta1, TGF beta 1R-I and TGF beta 1R-II, Smad-2 and Smad
-4 genes in all tumors. In our study, we confirmed the presence of reduced
levels of TGF beta1 in carcinomas. On the contrary, Smad-4 gene levels were
elevated in carcinomas when compared to that of adenomas. No significant d
ifferences were observed in gene expression of TGF beta 1RI and Smad-2. Our
results suggest that mutations of TGF beta1 receptors appear not to be inv
olved in adrenal tumorigenesis. Adrenal carcinomas showed a significant red
uction of the TGF beta1 mRNA levels but on the contrary Smad 4 mRNA levels
were significantly increased.