PTPH1 immunohistochemical expression and promoter methylation in breast cancer patients from India: A retrospective study.

Abstract

Protein Tyrosine Phosphatase H1/Protein Tyrosine Phosphatase Non receptor Type 3 (PTPH1/PTPN3) is upregulated and/or mutated in glioma, ovarian, gastric, and colorectal cancers. Previous studies have documented that PTPH1-associated breast cancers exhibit enhanced sensitivity to tamoxifen and tyrosine kinase inhibitors through dephosphorylation of ER and epidermal growth factor receptor, respectively. Owing to the key role that PTPH1 plays as a biomarker in predicting the response of chemotherapeutic drugs and lack of studies on Indian breast cancer patients, the present study investigated PTPH1 protein expression and its relationship to clinical features, ER/PR/HER2/neu statuses, and methylation of promoter in breast cancer tissues (n = 67) among Indian population by immunohistochemistry and methylation specific polymerase chain reaction. PTPH1 expression was upregulated in 58.21% (39/67) and downregulated in the rest of tumor specimens, and it correlated with ER, PR, and HER2/neu statuses with p values of <0.0001, 0.0113, and 0.0448, respectively. Additionally, we found that the 2 kb region upstream of PTPH1 gene harbored CpG sites within, and was ubiquitously methylated in breast cancer (n = 13), colon cancer tissue (n = 1), uterine cancer tissue (n = 1), normal breast tissue (n = 1) in addition to Hela and MCF7 cell lines. In conclusion, our data showed a strong correlation of the PTPH1 status with the ER and ubiquitous nature of PTPH1 promoter methylation at specific CpG sites irrespective of cancer types and protein expression. Our findings underscore the clinical relevance of PTPH1 expression in Indian patients and warrant additional studies to explore the importance of ubiquitously methylated promoter at specific CpG sites in upstream of the PTPH1 gene.

• Authors: Thejaswini Venkatesh, Abhishek Shetty, Shrijeet Chakraborti, Padmanaban S Suresh
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 234 Issue 2 Pg. 1071-1079 (02 2019) ISSN: 1097-4652 [Electronic] United States
• PMID: 30189107 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• Biomarkers, Tumor
• Receptors, Estrogen
• Receptors, Progesterone
• PTPN3 protein, human
• Protein Tyrosine Phosphatase, Non-Receptor Type 3

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (genetics, metabolism)
• Breast Neoplasms (enzymology, genetics)
• CpG Islands
• DNA Methylation
• Female
• HeLa Cells
• Humans
• Immunohistochemistry
• India
• MCF-7 Cells
• Middle Aged
• Polymerase Chain Reaction
• Predictive Value of Tests
• Promoter Regions, Genetic
• Protein Tyrosine Phosphatase, Non-Receptor Type 3 (genetics, metabolism)
• Receptors, Estrogen (metabolism)
• Receptors, Progesterone (metabolism)
• Retrospective Studies