Medicina (Buenos Aires)
versión On-line ISSN 1669-9106
GIACOMINI, D. et al. New mechanisms involved in the pathogenesis of pituitary adenomas. Medicina (B. Aires) [online]. 2003, vol.63, n.2, pp. 147-150. ISSN 1669-9106.
We studied Smad-4dn tumors generated from lactosomatotrophic GH3 cells stably transfected with a dominant negative form of Smad-4 (a bone morphogenetic protein-4, BMP-4, signal co-transducer) which had reduced tumorigenicity in nude mice, but had showed a late increase in tumor size. We found that they had lost in vivo the expression of Smad-4dn and had recovered c-Myc expression. In accordance, BMP-4 is overexpressed and stimulates the expression of c-Myc in human prolactinomas, but not in other human pituitary adenomas or normal pituitary. In adittion ICI 182,780 inhibited BMP-4 stimulated c-Myc expression and BMP-4 and 17b-estradiol in combination had an additive effect on GH3 cell proliferation. Their action was inhibited by blocking BMP-4 with ICI 182,780 or 17b-estradiol with Smad-4dn. Furthermore, co-immunoprecipitation studies demonstrate that Smad-4 physically interacts with the ERa/ERb. We show for the first time the role of BMP-4 in prolactinoma pathogenesis, involving a functional cross-talk BMP-4/E2.
Palabras clave : Prolactinoma; C-Myc.