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Elevation of SIPL1 (SHARPIN) Increases Breast Cancer Risk
1Division of Nephrology, Department of Medicine, McMaster University, Ontario, Canada; Father Sean O'Sullivan Research Institute, Ontario, Canada; The Hamilton Center for Kidney Research, St. Joseph's Hospital, Hamilton, Ontario, Canada.
Plos One
|May 21, 2015
Summary
Sharpin (SIPL1) gene amplification and elevated mRNA expression are linked to breast cancer development and progression. Higher SIPL1 levels correlate with poorer patient survival, particularly in certain subtypes, suggesting its role in tumorigenesis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Sharpin (SIPL1) is implicated in tumorigenesis, but its specific role in breast cancer is unclear.
- Understanding SIPL1's function is crucial for developing targeted breast cancer therapies.
Purpose of the Study:
- To investigate the association between SIPL1 gene amplification, expression, and breast cancer development.
- To explore the correlation of SIPL1 with breast cancer subtypes, grade, stage, and patient survival.
Main Methods:
- Systematic analysis of SIPL1 gene amplification and mRNA expression data from Oncomine datasets (17 studies, 3438 cases).
- Correlation analysis of SIPL1 gain with breast cancer grade and stage.
- Analysis of SIPL1 protein expression in 224 breast cancer cases using tissue microarrays.
- In vitro study on SIPL1 expression in MCF7 cells treated with progesterone.
Main Results:
- SIPL1 gene amplification and elevated mRNA expression were observed in invasive ductal breast cancers compared to normal tissues.
- Increased SIPL1 was found across various breast cancer subtypes (ER+, PR+, HER2+, triple-negative).
- SIPL1 gain correlated with higher tumor grade, and elevated mRNA with advanced stages and grades, predicting decreased patient survival, especially in PR+, ER+, or HER2- cancers.
- Higher SIPL1 protein levels correlated with ER+, PR+ tumors and AKT activation.
- Progesterone treatment reduced SIPL1 mRNA and protein in MCF7 cells.
Conclusions:
- SIPL1 gene amplification and overexpression are associated with breast cancer tumorigenesis and progression.
- SIPL1 is a potential biomarker for breast cancer aggressiveness and poor prognosis.
- The interaction between SIPL1 and progesterone may influence breast cancer development.
