Expression and prognostic role of SGTA in human breast carcinoma correlates with tumor cell proliferation

Abstract

Small glutamine-rich tetratricopeptide repeat-containing protein alpha (SGTA) was reported to be implicated in various cellular processes and involved in control of cell cycle regulation and transcription. It may play a critical role in oncogenesis. In this study, to investigate the potential roles of SGTA in breast cancer, expression patterns, interaction and the correlation with clinical/prognostic factors of SGTA and Ki-67 were examined among patients with breast cancer. Immunohistochemistry and Western blot analysis were performed for SGTA in 100 breast carcinoma samples. The data were correlated with clinicopathological features. The univariate and multivariate survival analyses were also performed to determine the prognostic significance. We found that SGTA was overexpressed in breast carcinoma compared with the adjacent normal tissues. High expression of SGTA was positively associated with histological grade (P = 0.002) and Ki-67 (P = 0.001). Univariate analysis showed that SGTA expression was associated with a poor prognosis (P = 0.002). Kaplan-Meier survival curves of the study population showed that high expression level of SGTA significantly correlated with short-term survival. While in vitro, SGTA depletion by small interfering RNA inhibited cell proliferation and cell cycle in breast cancer cell lines. Western blot analyses showed that SGTA depletion decreased cyclin A, cyclin B and CDK2, whereas increased p27 levels. Additionally, treatment of phosphatidylinositol 3-kinase inhibitor LY294002 could arrest cells growth and diminish SGTA expression. These results suggested that SGTA overexpression was involved in the pathogenesis of breast cancer which might serve as a future target for novel treatment in breast cancer.

TGFβ modulates inflammatory cytokines and growth factors to create premetastatic microenvironment and stimulate lung metastasis

“…Lung tissues were crushed in frozen state, and then extracted with protein lysis buffer containing 1 % NP-40, 20 mM Tris (pH 7.4), 137 mM NaCl, 10 % glycerol, and 1 mM phenylmethyl sulfonyl fluoride (Zhu et al 2014). Lysates were centrifuged at 14,0009g for 15 min at 4°C and total proteins were harvested.…”

Canine REIC/Dkk-3 interacts with SGTA and restores androgen receptor signalling in androgen-independent prostate cancer cell lines

“…These events suggest that the expression of SGTA is induced by the overexpression of chaperones in various cancers types, not only prostate cancer [e.g. , oesophageal squamous cell carcinoma and breast carcinoma] [31, 32]. Although upregulation of SGTA expression may not be related to hormonal signalling, overexpressed SGTA plays an important role as an inhibitor of AR signalling and confers the androgen-independent characteristics in prostate cancer [3].…”

The roles of cytosolic quality control proteins, SGTA and the BAG6 complex, in disease

“…Another disease linked to androgen signaling is breast cancer, one of the most common cancers among women. A 2014 study (Zhu et al, 2014) first examined the relationship between SGTA and breast cancer cells and found that SGTA was overexpressed in breast cancer cells compared to normal tissue. They also found a positive correlation between SGTA concentration and breast cancer cell proliferation following SGTA knockout experiments.…”

“…These results suggest that SGTA levels could be a potential indicator of breast cancer progression as concentration was found to increase at a higher histological grade. Additionally, SGTA was recognized as a potential prognosis indicator (Zhu et al, 2014). This leaves SGTA as an interesting potential treatment target for breast cancer and thus more research should be done into this relationship (Zhu et al, 2014).…”

“…Additionally, SGTA was recognized as a potential prognosis indicator (Zhu et al, 2014). This leaves SGTA as an interesting potential treatment target for breast cancer and thus more research should be done into this relationship (Zhu et al, 2014).…”