Abstract
Protein tyrosine phosphatase non-receptor type 12 (PTPN12) is a recently identified tumor suppressor gene (TSG) that is frequently compromised in human triple-negative breast cancer. In the present study, we investigated the expression of PTPN12 protein by patients with breast cancer in a Chinese population and the relationship between PTPN12 expression levels and patient clinicopathological features and prognosis. Additionally, we explored the underlying down-regulation mechanism from the perspective of an epigenetic alteration. We examined PTPN12 mRNA expression in five breast cancer cell lines using semi-quantitative reverse-transcription PCR, and detected PTPN12 protein expression using immunohistochemistry in 150 primary invasive breast cancer cases and paired adjacent non-tumor tissues. Methylation-specific PCR was performed to analyze the promoter CpG island methylation status of PTPN12. PTPN12 was significantly down-regulated in breast cancer cases (48/150) compared to adjacent noncancerous tissues (17/150; P < 0.05). Furthermore, low expression of PTPN12 showed a significant positive correlation with tumor size (P = 0.047), lymph node metastasis (P = 0.001), distant metastasis (P = 0.009), histological grade (P = 0.012), and survival time (P = 0.019). Additionally, promoter CpG island hypermethylation occurs more frequently in breast cancer cases and breast cancer cell lines with low PTPN12 expression. Our findings suggest that PTPN12 is potentially a methylation-silenced TSG for breast cancer that may play an important role in breast carcinogenesis and could potentially serve as an independent prognostic factor for invasive breast cancer patients.
Highlights
One million new cases of breast cancer are diagnosed each year worldwide and it is the most common neoplastic disease in women [1]
Recent reports have demonstrated that Protein tyrosine phosphatase non-receptor type 12 (PTPN12) inactivation leads to HER2/EGFR hyperactivity and cellular transformation in HER2-negative breast cancer and that PTPN12 is frequently compromised in human Triple-negative breast cancer (TNBC), indicating that it is potentially a new tumor suppressor gene (TSG) of TNBC [6]
We investigated whether promoter CpG island methylation is correlated with PTPN12 inactivation mechanisms using methylation-specific PCR (MSP)
Summary
One million new cases of breast cancer are diagnosed each year worldwide and it is the most common neoplastic disease in women [1]. Triple-negative breast cancer (TNBC), characterized by a lack of ER, PR, and HER2 expression, accounts for approximately 15~20% of the cases of all breast cancer types [2]. Accumulating evidence indicates that there is a correlation between PTPN12 and tumor development, including ovarian cancer, colon cancer, and prostate cancer [3,4,5]. Recent reports have demonstrated that PTPN12 inactivation leads to HER2/EGFR hyperactivity and cellular transformation in HER2-negative breast cancer and that PTPN12 is frequently compromised in human TNBC, indicating that it is potentially a new tumor suppressor gene (TSG) of TNBC [6]
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