Estrogens and insulin-like growth factor 1 modulate neoplastic cell growth in human cholangiocarcinoma. Academic Article uri icon

abstract

  • We investigated the expression of estrogen receptors (ERs), insulin-like growth factor 1 (IGF-1), and IGF-1R (receptor) in human cholangiocarcinoma and cholangiocarcinoma cell lines (HuH-28, TFK-1, Mz-ChA-1), evaluating the role of estrogens and IGF-1 in the modulation of neoplastic cell growth. ER-alpha, ER-beta, IGF-1, and IGF-1R were expressed (immunohistochemistry) in all biopsies (18 of 18) of intrahepatic cholangiocarcinoma. ER-alpha was expressed (Western blot) only by the HuH-28 cell line (intrahepatic cholangiocarcinoma), whereas ER-beta, IGF-1, and IGF-1R were expressed in the three cell lines examined. In serum-deprived HuH-28 cells, serum readmission induced stimulation of cell proliferation that was inhibited by ER and IGF-1R antagonists. 17beta-Estradiol and IGF-1 stimulated proliferation of HuH-28 cells to a similar extent to that of MCF7 (breast cancer) but greater than that of TFK-1 and Mz-ChA-1, inhibiting apoptosis and exerting additive effects. These effects of 17beta-estradiol and IGF-1 were associated with enhanced protein expression of ER-alpha, phosphorylated (p)-ERK1/2 and pAKT but with decreased expression of ER-beta. Finally, transfection of IGF-1R anti-sense oligonucleotides in HuH-28 cells markedly decreased cell proliferation. In conclusion, human intrahepatic cholangiocarcinomas express receptors for estrogens and IGF-1, which cooperate in the modulation of cell growth and apoptosis. Modulation of ER and IGF-1R could represent a strategy for the management of cholangiocarcinoma.

published proceedings

  • Am J Pathol

author list (cited authors)

  • Alvaro, D., Barbaro, B., Franchitto, A., Onori, P., Glaser, S. S., Alpini, G., ... Gaudio, E

citation count

  • 117

complete list of authors

  • Alvaro, Domenico||Barbaro, Barbara||Franchitto, Antonio||Onori, Paolo||Glaser, Shannon S||Alpini, Gianfranco||Francis, Heather||Marucci, Luca||Sterpetti, Paola||Ginanni-Corradini, Stefano||Onetti Muda, Andrea||Dostal, David E||De Santis, Adriano||Attili, Adolfo F||Benedetti, Antonio||Gaudio, Eugenio

publication date

  • September 2006