Abstract
BackgroundMortalin/GRP75 is a ubiquitous mitochondrial chaperone which related to the cytosolic heat shock protein 70 (HSP70), and plays a role in carcinogenesis. This study aims to investigate the Mortalin expression in breast cancer and its correlation with the outcome of the patients with breast cancer.MethodsA total of 155 invasive ductal carcinoma of breast patients with strict follow-up, 52 ductal carcinoma in situ (DCIS) and 45 adjacent non-tumor breast tissues were selected for immunohistochemical (IHC) staining of Mortalin protein. The localization of Mortalin protein was detected in MDA-MB231 breast cancer cells using immunofluorescence (IF) staining. The correlations between overexpression of Mortalin and the clinical features of patients with breast cancer were evaluated using chi-square test and Fisher’s exact tests. The survival rates were calculated by the Kaplan-Meier method, and the relationship between prognostic factors and patient survival was also analyzed by the Cox proportional hazard models.ResultsMortalin protein showed a mainly cytoplasmic staining pattern in breast cancers by using IHC staining in paraffin embedded breast cancer tissues and IF staining in MDA-MB231 breast cancer cells. The strongly positive rate of Mortalin protein was 63.9 % (99/155) in invasive ductal carcinoma of breast and was significantly higher than in DCIS 34.6 % (18/52) and adjacent non-tumor tissues 15.6 % (7/45). Overexpression of Mortalin was closely correlated with histological grade, clinical stage, lymph node metastasis, lower disease free survival (DFS) and overall survival (OS) rates of patients with breast cancer. Moreover, multivariate analysis suggested that Mortalin emerged as a significant independent prognostic factor along with clinical stage and Her2 expression status in patients with breast cancer.ConclusionsMortalin is upregulated in breast cancer, and may be a useful poor prognostic biomarker as well as a potential therapeutic target for patients with breast cancer.
Highlights
Mortalin/GRP75 is a ubiquitous mitochondrial chaperone which related to the cytosolic heat shock protein 70 (HSP70), and plays a role in carcinogenesis
In the current investigation, we focused on Mortalin/ mthsp70/GRP75, a member of the heat shock protein (Hsp) 70 family, which is enriched in human cancer cells [4, 9, 13]
We confirmed that the level of Mortalin was elevated in breast cancer, which supports the premise of overexpression of Mortalin in promoting human carcinogenesis
Summary
Mortalin/GRP75 is a ubiquitous mitochondrial chaperone which related to the cytosolic heat shock protein 70 (HSP70), and plays a role in carcinogenesis. In eastern China, which accounts for 38 % of the Chinese population, there has been a sharp increase in breast cancer incidence in recent decades [2]. Overexpression of Mortalin may interacts with the wild-type tumor suppressor protein p53 and modulates the Ras-Raf-MAPK pathway and increase the malignancy of tumor cells [6,7,8]. Wadhwa et al have shown that Mortalin is elevated in human brain tumor, colon carcinoma, leukemia, and the immortalized cell lines derived from the tumors [4]. It is associated with positive venous infiltration and advanced tumor TNM stages in Hepatocellular carcinoma [9]. Starenki et al found that Mortalin is upregulated in human medullary thyroid carcinoma tissues and its depletion robustly induces cell death and growth arrest in medullary thyroid carcinoma cell lines and mouse xenografts [10]
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