BACKGROUND: Of major interest for a better molecular understanding of pancreatic cancer is the EGF receptor family. While HER-1 (EGF-receptor) and HER-2 have been extensively studied, little is known about the clinical significance of HER-3 and especially HER-4 expression. METHODS: We investigated the expression of HER-1, HER-2, HER-3 and HER-4 in 11 pancreatic cancer cell lines using FACS-analysis and determined expression and overexpression of these receptors in 24 pancreatic cancer specimens. Therefore, we used two different immunostaining techniques: a highly sensitive streptavidin-biotin method showed receptor expression while an approximatly 10-fold less sensitive indirect immunperoxidase technique determined receptor-overexpression. RESULTS: HER-1 and HER-2 were expressed by all 11 pancreatic cancer cell lines, HER-3 was found in 82% and HER-4 in 54% of the cell lines. Low levels of HER-1, HER-2 and HER-3 were detected in all tumor samples but overexpression was only found in 33%, 25% and 50% of the cases, respectively. HER-4 was expressed by 37% of the tumor specimens but overexpression was seen in one patient only. HER-1 and HER-2 overexpression increased in parallel with the tumor stage and R0-resected tumors showed significantly less often overexpression compared to R1/R2 resected tumors (p < 0.05). In contrast, 54% of the R0-resected vs. 18% of the R1/R2 resected tumors showed HER-4 expression (p = 0.07) and HER-4 was exclusively found in non-metastatic tumors (p = 0.0149). CONCLUSION: Our data indicate that HER-1 and HER-2 overexpression contributes to a more aggressive phenotype. In contrast, the lack of HER-4 expression might increase the metastatic capacity of pancreatic cancer cells.
BACKGROUND: Of major interest for a better molecular understanding of pancreatic cancer is the EGF receptor family. While HER-1 (EGF-receptor) and HER-2 have been extensively studied, little is known about the clinical significance of HER-3 and especially HER-4 expression. METHODS: We investigated the expression of HER-1, HER-2, HER-3 and HER-4 in 11 pancreatic cancer cell lines using FACS-analysis and determined expression and overexpression of these receptors in 24 pancreatic cancer specimens. Therefore, we used two different immunostaining techniques: a highly sensitive streptavidin-biotin method showed receptor expression while an approximatly 10-fold less sensitive indirect immunperoxidase technique determined receptor-overexpression. RESULTS:HER-1 and HER-2 were expressed by all 11 pancreatic cancer cell lines, HER-3 was found in 82% and HER-4 in 54% of the cell lines. Low levels of HER-1, HER-2 and HER-3 were detected in all tumor samples but overexpression was only found in 33%, 25% and 50% of the cases, respectively. HER-4 was expressed by 37% of the tumor specimens but overexpression was seen in one patient only. HER-1 and HER-2 overexpression increased in parallel with the tumor stage and R0-resected tumors showed significantly less often overexpression compared to R1/R2 resected tumors (p < 0.05). In contrast, 54% of the R0-resected vs. 18% of the R1/R2 resected tumors showed HER-4 expression (p = 0.07) and HER-4 was exclusively found in non-metastatic tumors (p = 0.0149). CONCLUSION: Our data indicate that HER-1 and HER-2 overexpression contributes to a more aggressive phenotype. In contrast, the lack of HER-4 expression might increase the metastatic capacity of pancreatic cancer cells.
Authors: Christopher P Mill; Michael D Zordan; S Michael Rothenberg; Jeffrey Settleman; James F Leary; David J Riese Journal: Genes Cancer Date: 2011-08
Authors: Nicole M Davis; Melissa Sokolosky; Kristin Stadelman; Steve L Abrams; Massimo Libra; Saverio Candido; Ferdinando Nicoletti; Jerry Polesel; Roberta Maestro; Antonino D'Assoro; Lyudmyla Drobot; Dariusz Rakus; Agnieszka Gizak; Piotr Laidler; Joanna Dulińska-Litewka; Joerg Basecke; Sanja Mijatovic; Danijela Maksimovic-Ivanic; Giuseppe Montalto; Melchiorre Cervello; Timothy L Fitzgerald; Zoya Demidenko; Alberto M Martelli; Lucio Cocco; Linda S Steelman; James A McCubrey Journal: Oncotarget Date: 2014-07-15
Authors: Daniel Borja-Cacho; Eric Hans Jensen; Ashok Kumar Saluja; Donald J Buchsbaum; Selwyn Maurice Vickers Journal: Am J Surg Date: 2008-09 Impact factor: 2.565
Authors: Winnie S Liang; David W Craig; John Carpten; Mitesh J Borad; Michael J Demeure; Glen J Weiss; Tyler Izatt; Shripad Sinari; Alexis Christoforides; Jessica Aldrich; Ahmet Kurdoglu; Michael Barrett; Lori Phillips; Hollie Benson; Waibhav Tembe; Esteban Braggio; Jeffrey A Kiefer; Christophe Legendre; Richard Posner; Galen H Hostetter; Angela Baker; Jan B Egan; Haiyong Han; Douglas Lake; Edward C Stites; Ramesh K Ramanathan; Rafael Fonseca; A Keith Stewart; Daniel Von Hoff Journal: PLoS One Date: 2012-10-10 Impact factor: 3.240