[No authors listed]
Studies have revealed that genetic and functional aberrations of oncogenes, tumorâsuppressor genes, signaling pathways and receptors are among the most prominent events in pituitary tumorigenesis, and a potent biomarker would be helpful for early diagnosis, subsequent treatment and disease control. The present study investigated the expression signatures of solute carrier family 20 member 1, also known as phosphate transporter 1 (SLC20A1) and the Wnt/βâcatenin signaling pathway in 52 patients with somatotroph adenomas. According to immunohistochemistry analysis, the Hâscore of SLC20A1 was 222.6±15.2 in invasive tumor samples and 144.5±30.4 in nonâinvasive tumor samples (P<0.01), while the Hâscores of βâcatenin were 210.1±21.4 and 134.9±32.7, respectively (P<0.05). The Hâscores of Wnt inhibitory factor 1 (Wif1) exhibited the opposite trend, with scores of 134.5±22.7 and 253.6±14.8, respectively (P<0.01). The Hâscores of SLC20A1 were negatively associated with those of Wif1 in somatotroph adenomas (correlation coefficient r=â0.367). The mean progressionâfree survival in the low SLC20A1 group was longer than that in the group with high SLC20A1 Hâscores (P=0.024). Reverse transcriptionâquantitative PCR (RTâqPCR) and western blotting confirmed the interference efficiency of the segments short hairpin (Sh)âBâSLC20A1 and ShâCâSLC20A1. Cell proliferation experiments revealed that the cell viability of the ShâBâSLC20A1 group was 76.3±4.5, 65.7±3.7 and 53.1±3.2% of that of control GH3 cells after 24, 48 and 72 h of transfection, respectively, while the cell viability of the ShâCâSLC20A1 group was 86.4±5.7, 75.6±4.4 and 67.5±3.8%, respectively (P<0.05). ELISA analysis demonstrated the growth hormone (GH) levels in the ShâBâSLC20A1 and ShâCâSLC20A1 groups to be 34.7±10.4 and 54.6±14.4%, respectively, of that of control GH3 cells (P<0.05). The transmembrane invasion assay revealed that knocking down SLC20A1 signiï¬cantly suppressed cell invasion in the ShâBâSLC20A1 and ShâCâSLC20A1 groups. RTâqPCR and western blotting demonstrated that ShâBâSLC20A1 and ShâCâSLC20A1 evidently increased the levels of Wif1 and secreted frizzledârelated protein 4. The present data suggested that SLC20A1 levels are positively associated with tumor size, invasive behavior and tumor recurrence in somatotroph adenomas. Furthermore, SLC20A1 may be associated with the activation of the Wnt/βâcatenin signaling pathway.
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