Abstract
PELP1 acts as an estrogen receptor (ER) coactivator that exerts an essential role in the ER’s functions. ER coregulators have a critical role in the progression and response to hormonal treatment of estrogen-dependent tumors. We previously demonstrated that, in adrenocortical carcinoma (ACC), ERα is upregulated and that estradiol activates the IGF-II/IGF1R signaling pathways defining the role of this functional cross-talk in H295R ACC cell proliferation. The aim of this study was to determine if PELP1 is expressed in ACC and may play a role in promoting the interaction between ERα and IGF1R allowing the activation of pathways important for ACC cell growth. The expression of PELP1 was detected by Western blot analysis in ACC tissues and in H295R cells. H295R cell proliferation decrease was assessed by A3-(4,5-Dimethylthiaoly)-2,5-diphenyltetrazolium bromide (MTT) assay and [3H] thymidine incorporation. PELP1 is expressed in ACC tissues and in H295R cells. Moreover, treatment of H295R with E2 or IGF-II induced a multiprotein complex formation consisting of PELP1, IGF1R, ERα, and Src that is involved in ERK1/2 rapid activation. PELP1/ER/IGF1R/c-Src complex identification as part of E2- and IGF-II-dependent signaling in ACC suggests PELP1 is a novel and more efficient potential target to reduce ACC growth.
Highlights
Adrenocortical carcinomas (ACC) are rare and highly aggressive tumors, associated with a very poor prognosis, mostly due to a high risk of recurrence and limited therapeutic options [1]
PELP1 Is Expressed in Human adrenocortical carcinoma (ACC) Samples and in H295R Cells
Western we showed that PELP1 is expressed in normal normal
Summary
Adrenocortical carcinomas (ACC) are rare and highly aggressive tumors, associated with a very poor prognosis, mostly due to a high risk of recurrence and limited therapeutic options [1]. Complete surgical excision offers the best chance of long term survival but quite often, despite the complete resection, the tumor reinstates very recurrently [2]. The cause of adrenal cancer remains elusive, but studies in the past 10 years suggest genetic mutations in the adrenal gland lead to the initiation of a malignant tumor [3,4,5]. ACC is an extremely heterogeneous disease and the majority of currently published studies have analyzed only single pathways of signal transduction. It is becoming clear that ACC pathogenesis involves integration of signals and the interplay of downstream pathways. The IGF system and estrogen-dependent pathways appear to be of particular interest
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