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An In Vitro Dormancy Model of Estrogen-sensitive Breast Cancer in the Bone Marrow: A Tool for Molecular Mechanism Studies and Hypothesis Generation
Published on: June 30, 2015
Suppression of ING1 expression in sporadic breast cancer
1Departments of Biochemistry & Molecular Biology and Oncology and Southern Alberta Cancer Research Centre, Faculty of Medicine, The University of Calgary, 3330 Hospital Drive, NW, Calgary, Alberta T2N 4N1, Canada.
Abstract:
Down regulation of the ING1 candidate tumour suppressor promotes growth in soft agar and focus formation in vitro and tumour formation in vivo. ING1 encodes a nuclear, cell cycle-regulated protein, overexpression of which efficiently blocks cell growth and is capable of inducing apoptosis in different experimental systems. Here we present the first report of ING1 mutation and expression analysis in a total of 452 cancer samples. One germline missense alteration and three germline silent alterations were detected in 377 primary breast cancers while marked (2 - 10-fold) decreases in ING1 mRNA expression were seen in 44% of primary breast cancers and in ten of ten breast cancer cell lines examined. Furthermore, the majority of breast cancers (58%) showing decreased ING1 expression had metastasized to regional lymph nodes whereas only 9% of cancers with elevated ING1 expression, compared to adjacent normal tissues, were metastatic. Thus, ING1 mutation is very rare in breast or ovarian cancers, however, repression of ING1 expression frequently accompanies tumour development of breast cancer.
Insights
Down regulation of the ING1 gene, a tumor suppressor, promotes cancer growth. Reduced ING1 expression is common in breast cancers and linked to metastasis, suggesting its role in tumor development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The ING1 gene encodes a nuclear protein that regulates the cell cycle and can induce apoptosis.
- Down-regulation of ING1's tumor suppressor function is associated with increased cancer cell growth and tumor formation.
Purpose of the Study:
- To investigate the mutation and expression of the ING1 gene in breast and ovarian cancers.
- To determine the correlation between ING1 expression levels and breast cancer metastasis.
Main Methods:
- Analysis of ING1 mutations and mRNA expression in 452 cancer samples, including 377 primary breast cancers.
- Comparison of ING1 expression in breast cancer tissues and cell lines with adjacent normal tissues.
- Correlation analysis between ING1 expression levels and lymph node metastasis in breast cancer patients.
Main Results:
- ING1 mutations were rare in breast and ovarian cancers.
- Marked decreases in ING1 mRNA expression were observed in 44% of primary breast cancers and all tested breast cancer cell lines.
- A significant association was found between decreased ING1 expression and lymph node metastasis in breast cancers (58% vs. 9% with elevated expression).
Conclusions:
- ING1 mutations are infrequent in breast and ovarian cancers.
- Repression of ING1 expression is a common event in breast cancer development.
- Reduced ING1 expression is strongly correlated with increased metastatic potential in breast cancer, highlighting its role as a tumor suppressor.
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