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SEL1L expression decreases breast tumor cell aggressiveness in vivo and in vitro
Rosaria Orlandi1, Monica Cattaneo, Flavia Troglio
1Molecular Targeting Unit, Department of Experimental Oncology, Istituto Nazionale Tumori, 20133 Milan, Italy.
Abstract:
SEL1L, the human orthologue of the Caenorhabditis elegans sel-1 gene, is differentially expressed in breast primary tumors and in normal breast tissues. Analysis of a series of human primary breast carcinomas, using a monoclonal antibody raised against a SEL1L recombinant protein, revealed down-modulation or absence of SEL1L expression in about two-thirds of the tumors as compared with normal breast epithelial cells. Overall survival analysis of breast carcinoma patients indicated a statistically significant correlation between SEL1L down-modulation and poor prognosis. MCF-7, human breast carcinoma cells, were transfected with a construct containing the entire SEL1L cDNA driven by an inducible promoter and showed a dramatic reduction in anchorage-dependent growth and colony formation in soft agar. Growth of the transfected cells in Matrigel, an extracellular matrix rich with laminin, restored colony-formation ability. These results point to the role for SEL1L in breast tumor growth and aggressiveness, possibly involving cell-matrix interactions.
Insights
SEL1L expression is reduced in most breast tumors, correlating with poor patient prognosis. Restoring SEL1L in cancer cells inhibits growth, suggesting its role in breast cancer aggressiveness and cell-matrix interactions.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- SEL1L, the human orthologue of C. elegans sel-1, shows differential expression in breast tissues.
- Its role in breast cancer development and progression is not fully understood.
Purpose of the Study:
- To investigate the expression pattern of SEL1L in human breast carcinomas.
- To determine the correlation between SEL1L expression levels and patient prognosis.
- To elucidate the functional role of SEL1L in breast cancer cell growth and behavior.
Main Methods:
- Monoclonal antibody-based analysis of SEL1L expression in primary breast tumors and normal tissues.
- Survival analysis of breast carcinoma patients.
- Transfection of MCF-7 breast cancer cells with SEL1L cDNA and assessment of growth in vitro and in Matrigel.
Main Results:
- SEL1L expression was down-modulated or absent in approximately two-thirds of primary breast tumors compared to normal breast epithelial cells.
- Down-modulation of SEL1L significantly correlated with poor overall survival in breast carcinoma patients.
- Inducible expression of SEL1L in MCF-7 cells dramatically reduced anchorage-dependent growth and soft agar colony formation.
- Growth in Matrigel partially restored colony-formation ability in SEL1L-expressing cells.
Conclusions:
- SEL1L plays a significant role in breast tumor growth and aggressiveness.
- SEL1L may influence breast cancer progression through mechanisms involving cell-matrix interactions.
- SEL1L down-modulation serves as a potential prognostic marker for breast cancer.