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Effect of mts1 (S100A4) expression on the progression of human breast cancer cells
M Grigorian1, N Ambartsumian, A E Lykkesfeldt
1Danish Cancer Society, Copenhagen.
Abstract:
The mts1 (S100A4) gene, encoding a Ca(2+)-binding protein of the S-100 subfamily, is involved in the control of tumor metastasis in some murine tumor cell lines. To further analyze its role, we transfected hormone-responsive human breast cancer MCF-7 cells with the mts1 gene under the control of a strong constitutive promoter. All of the 3 tested clones (MCF-7/mts1) producing Mts1 protein acquired an ability for hormone-independent growth in nude mice. Tumors derived from mts1 transfectants revealed local invasiveness into surrounding muscle and adipose tissues and metastasized to regional lymph nodes and lungs, characteristics which are rarely observed with parental MCF-7 cells. Electron-microscopic analysis of MCF-7/mts1 cells demonstrated structural changes in anchoring junctions, particularly in intermediate filament attachment site (desmosomes). The mts1-transfected clones expressed estrogen receptor, and their growth in tissue culture was both estrogen- and anti-estrogen responsive. Changes in regulation of the estrogen-dependent proteins progesterone receptor and cathepsin D were observed in some of the transfected clones. Our results indicate that mts1 expression in human breast cancer cells induces several changes characteristic of malignant phenotype and tumor progression.
Insights
The mts1 gene promotes malignant progression in human breast cancer. Its expression induced hormone-independent growth, invasiveness, and metastasis in MCF-7 cells, indicating a role in tumor progression.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- The mts1 (S100A4) gene encodes a calcium-binding protein implicated in tumor metastasis.
- Understanding mts1's role in human breast cancer progression is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the functional role of mts1 gene expression in human breast cancer cells.
- To analyze the impact of mts1 transfection on MCF-7 cell behavior and tumor characteristics.
Main Methods:
- Transfection of hormone-responsive human breast cancer MCF-7 cells with the mts1 gene.
- In vivo tumor growth and metastasis assessment in nude mice.
- Electron microscopy to analyze cellular structural changes.
- Hormone responsiveness assays in tissue culture.
Main Results:
- MCF-7 cells transfected with mts1 (MCF-7/mts1) exhibited hormone-independent growth in vivo.
- Mts1-expressing tumors showed increased local invasiveness and metastasis to lymph nodes and lungs.
- Structural alterations in desmosomes were observed in MCF-7/mts1 cells.
- Transfected cells remained responsive to estrogen and anti-estrogen treatments, with altered regulation of progesterone receptor and cathepsin D.
Conclusions:
- Mts1 gene expression induces a malignant phenotype in human breast cancer cells.
- Mts1 plays a significant role in promoting tumor progression, invasiveness, and metastasis.
- The findings highlight mts1 as a potential therapeutic target in breast cancer.