Expression of Estrogen-Induced Genes and Estrogen Receptor β in Pancreatic Neuroendocrine Tumors

Abstract

Objective The indolent nature and expression of progesterone receptor (PR), a well-known estrogen-induced gene, in a subset of pancreatic neuroendocrine tumors (PanNETs), raise the possibility of hormonal regulation in these tumors. Methods Immunohistochemical expression of estrogen receptors (ER) α and β and mRNA expression of estrogen-induced genes (PR, EIG121, IGF-1, IGF-1R, sFRP1, and sFRP4) by qRT-PCR were examined in 131 WHO G1-G2 PanNETs and correlated expression with clinicopathologic features. Results 39 PanNETs (30%) showed high positive ERβ staining and 87 cases (66%) had low positive ERβ staining; only 5 cases (4%) had no nuclear staining. PanNETs with small size (P=.02), low WHO grade (P=.02) and low AJCC stage (P=.006) more frequently showed high positive ERβ staining. Among estrogen-induced genes studied, PanNETs had significantly higher expression of PR, EIG121, IGF-1, sFRP1, and sFRP4 compared to normal pancreas, independent of age or gender. High positive ERβ staining was associated with increased expression of PR (P < .001) and EIG121 (P=.02). Conclusions Our study showed that PanNETs with favorable prognostic features have higher ERβ expression, which is associated with upregulated PR and EIG121 mRNA expression. Estrogen regulation in PanNETs could potentially help in risk stratification and provide a rational target for novel treatment strategies.

KIAA1324 Suppresses Gastric Cancer Progression by Inhibiting the Oncoprotein GRP78

“…The role of KIAA1324 in cancer has been evaluated only in endometrial, pancreatic, and ovarian cancer to date (21)(22)(23). In type I endometrial cancer, KIAA1324 expression is higher at early stage than that of benign tumors, but reduced in high grade and stage endometrial carcinoma.…”

“…The correlation between KIAA1324 expression and prognosis in endometrial, ovarian, and pancreatic cancer patients was previously reported (21)(22)(23), but the role of KIAA1324 in gastric cancer has not been investigated yet. Deng and colleagues demonstrated that KIAA1324 localizes at the plasma membrane and endomembranes and is involved in autophagy (24).…”

Is estrogen exposure a protective factor for pancreatic neuroendocrine tumours in female patients with multiple endocrine neoplasia syndrome type 1?

“…A recent study by Estrella et al . suggested that PNET patients with favourable prognostic features had higher ERβ expression.…”

<b>Papel da insulina sobre a esteroidogênese no corpo lúteo canino</b>

“…The CYP1B1 codes a cytochrome P450 enzyme responsible of producing a cathecol estrogen, which is a strong agonist of estrogen receptors (PICCINATO et al, 2016) and its expression was higher on day 10 p.o, decreased afterwards, but increased again during regression (days 50 and 60 p.o). Whereas KIAA1324, an estrogen regulated gene (ESTRELLA et al, 2014), was more expressed during regression. The encoded protein has been characterized as a transmembrane protein, which is related to autophagic vacuole formation (DENG et al, 2010) and in pancreatic tumor cells its expression may be regulated by ERβ (ESTRELLA et al, 2014).…”

“…Whereas KIAA1324, an estrogen regulated gene (ESTRELLA et al, 2014), was more expressed during regression. The encoded protein has been characterized as a transmembrane protein, which is related to autophagic vacuole formation (DENG et al, 2010) and in pancreatic tumor cells its expression may be regulated by ERβ (ESTRELLA et al, 2014). Thus, these results suggest a role of E2 during CL formation and regression.…”