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SLC12A7 Amplifications Promote Adrenocortical Cancer Cell Invasiveness
*Taylor C Brown, *Timothy D Murtha, *Reju Korah, *Tobias Carling
Yale University School of Medicine, Department of Surgery, New Haven, CT

Objective: Solute Carrier Family 12 Member 7 (SLC12A7) promotes tumor metastasis and its amplification portends a poor prognosis in cancer. SLC12A7 amplifications were recently discovered in adrenocortical carcinoma (ACC) tumors. This study determines the in vitro effects of upregulated SLC12A7 expression on ACC tumor cell line SW-13.
Design: Basic science.
Setting: Laboratory.
Patients: None.
Interventions: Gene expression analysis demonstrated normal SLC12A7 expression levels in SW-13 cells. SW-13 cells were stably transfected with pCMV6-Entry/SLC12A7 expression vector (SW-13/S) to determine the effects of enforced overexpression of SLC12A7. SW-13 cells stably transfected with empty pCMV6-Entry vector and parental cells served as controls. In vitro studies tested the outcomes of SLC12A7 overexpression on malignant characteristics, including cell viability, growth, potential for clonogenic growth, motility, invasion, and cell adhesion and detachment kinetics. Microscopic analysis assessed morphological changes imparted by SLC12A7 overexpression. Transcription factor gene expression array analysis was performed to identify potential downstream mediators of SLC12A7 overexpression.
Main outcome measures: Cell viability, growth, clonogenic growth, migration, invasion, adhesion and detachment kinetics, morphological changes, and transcription factor expression alterations.
Results: SLC12A7 overexpression did not influence cell viability, growth, or clonogenic growth potential. Enforced SLC12A7 overexpression, however, robustly promoted motility and invasion characteristics (p<0.05). SW-13/S cells also showed significantly increased cell attachment and detachment turnover (p<0.05), potentially propelled by increased filopodia formation. Differential transcription factor expression analysis identified Inhibitor of DNA Binding 1 (ID1) as a potential modulator of SLC12A7 induced malignant activity.
Conclusions: Amplification of SLC12A7 observed in adrenocortical carcinoma is shown here in vitro to exacerbate the malignant behavior of ACC cells, possibly mediated in part by ID1. These findings suggest SLC12A7 as a potential therapeutic target in ACC.


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