Anti-c-myc efficacy block EGFL7 induced prolactinoma tumorigenesis

Abstract

Resistance to Dopamine agonists therapy is still a key factor that hinders the clinical treatment of prolactinoma. Consequently, a large number of investigations have been carried out to identify novel therapeutic targets. Our previous studies have suggested that the epidermal growth factor-like domain 7 (EGFL7) plays a crucial role in tumorigenesis of pituitary adenomas via EGFR/AKT/MAPK signaling pathway. In the present research, we found a positive staining of c-myc intimately associated with high-level EGFL7 in invasive prolactinoma compared to non-invasive prolactinoma and the normal pituitary gland. Meanwhile, PI3K/Akt and MAPK signaling cascades closely related to the activation of c-myc. Therefore, this research was conducted to explore the cooperation effect of c-myc and EGFL7 in prolactinoma. The inhibition of c-myc with anti-c-myc antibodies significantly reduced the proliferation, PRL secretion and invasion of rat prolactinoma MMQ cells. Notably, down regulation c-Myc by in vitro administration of anti-c-Myc antibodies could significantly depress EGFL7 induced MMQ cell proliferation, PRL secretion and invasion. An anti-c-Myc antibody could block EGFL7 induced Akt activation, but the expression of p-ERK was not altered by an anti-c-Myc antibody. Thus, our results suggest that anti-c-myc efficacy could block EGFL7 induced prolactinoma tumorigenesis via inhibited Akt activation in MMQ cells.