TY - JOUR
T1 - SEL1L expression in pancreatic adenocarcinoma parallels SMAD4 expression and delays tumor growth in vitro and in vivo
AU - Cattaneo, Monica
AU - Orlandini, Simonetta
AU - Beghelli, Stefania
AU - Moore, Patrick S.
AU - Sorio, Claudio
AU - Bonora, Antonio
AU - Bassi, Claudio
AU - Talamini, Giorgio
AU - Zamboni, Giuseppe
AU - Orlandi, Rosaria
AU - Ménard, Sylvie
AU - Bernardi, Luigi Rossi
AU - Biunno, Ida
AU - Scarpa, Aldo
PY - 2003/9/25
Y1 - 2003/9/25
N2 - Recent data suggest that SEL1L may play an important role in pancreatic carcinoma, similar to breast cancer, where the expression of SEL1L has been associated with a reduction in both proliferative activity in vitro and clinical tumor aggressiveness. To investigate this possibility, we examined the expression of Sel1L in a series of primary pancreatic carcinomas by immunohistochemistry and characterized the effects of Sel1L overexpression both in vitro and in vivo. In 74 pancreatic cancers analysed, 36% lacked Sel1L expression, although there was no significant correlation between the expression of Sel1L and any clinicopathologic parameter, including survival. However, immunohistochemical reactivity for Sel1L and Dpc4/ Smad4 was concordant in 69% of cases (χ2 test P <0.004). Overexpression of SEl1L in stably transfected pancreatic cancer cells caused both a decrease in clonogenicity and anchorage-independent growth as well as a significant increase in the levels of activin A and SMAD4. When implanted in nude mice, Suit-2-SEL1L-overexpressing clones displayed a considerably reduced rate of tumor growth. Thus, it can be hypothesized that Sel1L plays an important function in the growth and aggressiveness of pancreatic carcinoma. Moreover, our data provide evidence that SEL1L has an impact on the expression of genes involved in regulation of cellular growth, possibly through the TGF-β signaling pathway.
AB - Recent data suggest that SEL1L may play an important role in pancreatic carcinoma, similar to breast cancer, where the expression of SEL1L has been associated with a reduction in both proliferative activity in vitro and clinical tumor aggressiveness. To investigate this possibility, we examined the expression of Sel1L in a series of primary pancreatic carcinomas by immunohistochemistry and characterized the effects of Sel1L overexpression both in vitro and in vivo. In 74 pancreatic cancers analysed, 36% lacked Sel1L expression, although there was no significant correlation between the expression of Sel1L and any clinicopathologic parameter, including survival. However, immunohistochemical reactivity for Sel1L and Dpc4/ Smad4 was concordant in 69% of cases (χ2 test P <0.004). Overexpression of SEl1L in stably transfected pancreatic cancer cells caused both a decrease in clonogenicity and anchorage-independent growth as well as a significant increase in the levels of activin A and SMAD4. When implanted in nude mice, Suit-2-SEL1L-overexpressing clones displayed a considerably reduced rate of tumor growth. Thus, it can be hypothesized that Sel1L plays an important function in the growth and aggressiveness of pancreatic carcinoma. Moreover, our data provide evidence that SEL1L has an impact on the expression of genes involved in regulation of cellular growth, possibly through the TGF-β signaling pathway.
KW - Adenocarcinoma
KW - DPC4/Smad4
KW - Pancreas
KW - SEL1L
KW - TGFβ-pathway
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U2 - 10.1038/sj.onc.1206665
DO - 10.1038/sj.onc.1206665
M3 - Article
C2 - 14508516
AN - SCOPUS:0142135502
VL - 22
SP - 6359
EP - 6368
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 41
ER -