Related Experiment Video
Updated: Jul 9, 2026
Inducible and Reversible Dominant-negative (DN) Protein Inhibition
Published on: January 7, 2019
RIN1 is a breast tumor suppressor gene
Marc Milstein1, Chelsea K Mooser, Hailiang Hu
1Department of Biological Chemistry, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA.
Abstract:
Breast cancer progression is driven by altered gene expression. We show that the RIN1 gene, which encodes a RAS effector regulating epithelial cell properties, is silenced in breast tumor cell lines compared with cultured human mammary epithelial cells. We also report that RIN1 is often reduced in human breast tumor cells compared with morphologically normal breast glandular cells. At least two silencing mechanisms seem to be involved. Overexpression of the transcription repressor SNAI1 (Snail) was observed in ZR75-1 cells, and SNAI1 knockdown restored RIN1 expression. In addition, DNA methylation within the RIN1 promoter and the first exon in KPL-1 cells suggested that epigenetic modifications may contribute to silencing, and demethylation was shown to restore RIN1 expression. Reexpression of RIN1 was shown to inhibit anchorage-independent growth in soft agar. In addition, RIN1 expression inhibited both the initiation and progression of tumorigenesis for two breast tumor cell lines in a mouse model, consistent with a tumor suppressor function. We also show that RIN1 acts as a negative regulator of tumor cell invasive growth and that this requires the ABL kinase-signaling function of RIN1, suggesting a mechanism through which RIN1 silencing may contribute to breast cancer progression.
Insights
The RIN1 gene is silenced in breast cancer, acting as a tumor suppressor. Restoring RIN1 expression inhibits tumor growth and invasion, suggesting its loss contributes to breast cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Breast cancer progression is linked to changes in gene expression.
- The RIN1 gene, a RAS effector, influences epithelial cell characteristics.
Purpose of the Study:
- To investigate the role of RIN1 in breast cancer.
- To identify mechanisms of RIN1 silencing and its functional consequences.
Main Methods:
- Comparison of RIN1 expression in breast tumor cell lines and normal mammary epithelial cells.
- Analysis of gene silencing mechanisms including transcription repressor SNAI1 (Snail) and DNA methylation.
- Assessment of RIN1 re-expression effects on anchorage-independent growth and tumor development in a mouse model.
- Investigation of RIN1's role in regulating tumor cell invasion via ABL kinase signaling.
Main Results:
- RIN1 is silenced in breast tumor cell lines and reduced in human breast tumor cells.
- SNAI1 overexpression and DNA methylation were identified as RIN1 silencing mechanisms.
- RIN1 re-expression inhibited anchorage-independent growth and suppressed tumor initiation and progression in vivo.
- RIN1 negatively regulates tumor cell invasive growth, dependent on its ABL kinase-signaling function.
Conclusions:
- RIN1 functions as a tumor suppressor in breast cancer.
- Silencing of RIN1, through epigenetic or transcriptional mechanisms, promotes breast cancer progression and invasion.
- Restoring RIN1 expression represents a potential therapeutic strategy for breast cancer.
Related Concept Videos
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
02:38The Ras Gene
Ras is a superfamily...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...