Related Experiment Video
Updated: May 31, 2026
Genetic Profiling and Genome-Scale Dropout Screening to Identify Therapeutic Targets in Mouse Models of Malignant Peripheral Nerve Sheath Tumor
Published on: August 25, 2023
An extensive tumor array analysis supports tumor suppressive role for nucleophosmin in breast cancer
Piia-Riitta Karhemo1, Antti Rivinoja, Johan Lundin
1Research Programs Unit, Molecular Cancer Biology, and Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
Abstract:
Nucleophosmin (NPM) is a multifunctional protein involved in a complex network of interactions. The role of NPM in oncogenesis is controversial. The NPM gene (NPM1) is mutated or rearranged in a number of hematological disorders, but such changes have not been detected in solid cancers. However, experiments with cultured NPM-null cells and with mice carrying a single inactivated NPM allele indicate a tumor suppressor function for NPM. To resolve the role of NPM in solid cancers, we examined its expression and localization in histologically normal breast tissue and a large array of human breast carcinoma samples (n = 1160), and also evaluated its association with clinicopathological variables and patient survival. The intensity and localization (nucleolar, nuclear, cytoplasmic) of NPM varied across clinical samples. No mutations explaining the differences were found, but the present findings indicate that expression levels of NPM affected its localization. Our study also revealed a novel granular staining pattern for NPM, which was an independent prognostic factor of poor prognosis. In addition, reduced levels of NPM protein were associated with poor prognosis. Furthermore, luminal epithelial cells of histologically normal breast displayed high levels of NPM and overexpression of NPM in the invasive MDA-MB-231 cells abrogated their growth in soft agar. These results support a tumor suppressive role for NPM in breast cancer.
Insights
Nucleophosmin (NPM) acts as a tumor suppressor in breast cancer. Reduced NPM levels and a novel granular staining pattern indicate a poor prognosis for patients.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Nucleophosmin (NPM) is a multifunctional protein with a debated role in oncogenesis.
- While NPM1 gene mutations are found in hematological disorders, they are absent in solid cancers.
- Previous studies suggest NPM may function as a tumor suppressor.
Purpose of the Study:
- To investigate the role of Nucleophosmin (NPM) in solid cancers, specifically breast cancer.
- To examine NPM expression, localization, and association with clinicopathological variables and patient survival in breast carcinoma.
- To clarify the controversial role of NPM in oncogenesis.
Main Methods:
- Analysis of NPM expression and localization in 1160 human breast carcinoma samples and normal breast tissue.
- Evaluation of the association between NPM levels/localization and clinicopathological variables.
- Assessment of NPM's prognostic significance and its effect on breast cancer cell growth in vitro.
Main Results:
- NPM expression intensity and localization (nucleolar, nuclear, cytoplasmic) varied significantly across clinical samples.
- No NPM gene mutations were detected, but expression levels influenced NPM localization.
- A novel granular NPM staining pattern emerged as an independent predictor of poor prognosis.
- Reduced NPM protein levels correlated with unfavorable patient outcomes.
- High NPM levels in normal breast luminal epithelial cells and NPM overexpression inhibiting MDA-MB-231 cell growth in soft agar suggest a tumor-suppressive function.
Conclusions:
- Nucleophosmin (NPM) exhibits tumor-suppressive properties in breast cancer.
- NPM expression levels and localization are critical for its function.
- A novel granular NPM staining pattern and reduced NPM levels are associated with poor prognosis in breast cancer patients.
Related Concept Videos
02:55The Nucleolus
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...
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...
02:23Abnormal Proliferation
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...