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Heterogeneity Mapping of Protein Expression in Tumors using Quantitative Immunofluorescence
Published on: October 25, 2011
Expression of tropomyosin isoforms in benign and malignant human breast lesions
1Unit of Cell and Molecular Analysis, Karolinska Institute and Hospital, Stockholm, Sweden.
Abstract:
High molecular weight tropomyosins (tms) are commonly down-regulated in fibroblasts transformed by oncogenes. Previous studies have also demonstrated that specific tm isoforms are down-regulated in human breast carcinoma cell lines. We examined tropomyosin isoforms in cells prepared from non-cancerous breast lesions and primary human breast carcinomas. The average level of expression of all three high molecular weight tm isoforms (tm 1-3) in carcinomas was generally found to be less than 25% of that observed in non-cancerous breast lesions. Interestingly, the expression of tm 1 was found to be 1.7-fold higher in primary tumours with metastatic spread to axillary lymph nodes compared with primary tumours with no evidence of metastasis (p<0.05). Similarly, tm 1 expression was higher in two 12V-H-ras transformed fibroblast cell lines capable of experimental metastasis compared with three weakly metastatic cell lines. We conclude from these studies that expression of high molecular weight tm isoforms is low in primary breast carcinomas, and that metastatic tumours express relatively high levels of tm 1.
Insights
High molecular weight tropomyosins (TMs) are significantly reduced in breast cancer cells. However, tropomyosin 1 (TM1) expression increases in metastatic breast tumors, suggesting a role in cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- High molecular weight tropomyosins (TMs) are frequently downregulated in oncogene-transformed fibroblasts.
- Specific TM isoforms show reduced expression in human breast carcinoma cell lines.
Purpose of the Study:
- To investigate tropomyosin isoform expression in non-cancerous breast lesions and primary human breast carcinomas.
- To determine the correlation between TM expression and breast cancer metastasis.
Main Methods:
- Analysis of tropomyosin isoform levels in tissue samples from non-cancerous breast lesions and primary breast carcinomas.
- Comparison of TM expression in primary tumors with and without lymph node metastasis.
- Evaluation of TM1 expression in 12V-H-ras transformed fibroblast cell lines with varying metastatic potential.
Main Results:
- Average expression of high molecular weight TM isoforms (TM 1-3) in carcinomas was less than 25% of that in non-cancerous lesions.
- TM1 expression was 1.7-fold higher in primary tumors with metastatic spread to axillary lymph nodes (p<0.05).
- TM1 expression was elevated in highly metastatic fibroblast cell lines compared to weakly metastatic ones.
Conclusions:
- High molecular weight TM isoforms are generally downregulated in primary breast carcinomas.
- Metastatic breast tumors exhibit relatively high levels of TM1 expression.
- TM1 may play a role in promoting breast cancer metastasis.

