Significantly increased cortisol secretion in normal adrenocortical cells transfected with K-ras mutants derived from human functional adrenocorticaltumors

Citation
Ch. Hsu et al., Significantly increased cortisol secretion in normal adrenocortical cells transfected with K-ras mutants derived from human functional adrenocorticaltumors, DNA CELL B, 20(4), 2001, pp. 231-238
Citations number
36
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
DNA AND CELL BIOLOGY
ISSN journal
1044-5498 → ACNP
Volume
20
Issue
4
Year of publication
2001
Pages
231 - 238
Database
ISI
SICI code
1044-5498(200104)20:4<231:SICSIN>2.0.ZU;2-N
Abstract
Our previous study showed that the mutation hotspots of the K-ras proto-onc ogene in human functional adrenocortical tumors are in codons 15, 16, 18, a nd 31, thus differing from the sites in other tumors. In addition, analyzin g the K-Ras protein by a recombinant DNA technique showed that the activity of endogenic GTPase and the GTPase-activating protein (GAP)-binding abilit y were significantly decreased in patients with these tumors. The aim of th is study was to understand whether those K-ras mutants, which mere found on ly in human adrenocortical tumors, play an important role in these tumors. Thus, the mutant K-ras cDNA was constructed with mammalian expression vecto rs and transfected into normal adrenocortical cells. The amount of cortisol secreted by the transfected cells was 20 to 30 times that of normal cells. Furthermore, Northern blot analysis revealed that the expression of the th ree steroidogenesis-related genes P450(scc) (cholesterol sidechain cleavage enzyme), P450(C17) (17 alpha -hydroxylase/17, 20-lyase), and P450(C21) (st eroid 21-hydroxylase) gene increased in the transfected cells. The K-ras on cogene significantly increases cortisol secretion by normal adrenocortical cells.