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Expression of transforming growth factor-beta1 and transforming growth factor-beta Type-II receptor mRNA in papillary
H Matoba1, S Sugano, N Yamaguchi
1First Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
Abstract:
Transforming growth factor-beta1 (TGF-beta1) is a potent inhibitor of epithelial cell proliferation. Signal transduction by TGF-beta1 involves direct binding to the TGF-beta Type-II receptor and then the formation of a heterodimeric complex of TGF-beta Type-I and Type-II receptor. To explore the role of TGF-beta1 in thyroid carcinoma, we examined the expression of TGF-beta1 and TGF-beta Type-II receptor mRNA by northern blotting analysis in both 14 papillary thyroid carcinomas and surrounding normal thyroid tissues. Relative mRNA level was determined by scanning densitometry of the autoradiogram and corrected for loading differences using a human beta-actin cDNA probe. The relative mRNA levels of TGF-beta1 in 12 out of 14 papillary thyroid carcinomas were higher than those in surrounding normal thyroid tissues. In contrast, the relative mRNA levels of TGF-beta Type-II receptor were reduced to 60.1+/-18.3% of those of normal thyroid tissues in 10 papillary thyroid carcinomas. There were no clear relationships between the relative mRNA levels for TGF-beta1 and TGF-beta Type-II receptor and the histological characteristics of papillary thyroid carcinomas. The relative mRNA levels for TGF-beta1 and TGF-beta Type-II receptor did not show significant differences in thyroid carcinomas with or without lymph node metastases. There was a negative correlation between the TGF-beta Type-II receptor mRNA level and tumor size, while no significant correlation was observed between the TGF-beta1 mRNA level and tumor size. In conclusion, most papillary thyroid carcinomas overexpress TGF-beta1 mRNA but exhibit a reduction in TGF-beta Type-II receptor mRNA. The reduction of TGF-beta Type-II receptor mRNA may play a role in the pathogenesis of papillary thyroid carcinoma.
Insights
Most papillary thyroid carcinomas overexpress transforming growth factor-beta1 (TGF-beta1) mRNA but show reduced TGF-beta Type-II receptor mRNA. This suggests a potential role for TGF-beta Type-II receptor in thyroid cancer development.
Area of Science:
- Molecular Biology
- Oncology
- Cell Signaling
Background:
- Transforming growth factor-beta1 (TGF-beta1) is a known inhibitor of epithelial cell proliferation.
- TGF-beta1 signaling is initiated by binding to the TGF-beta Type-II receptor, forming a complex with the TGF-beta Type-I receptor.
Purpose of the Study:
- To investigate the expression of TGF-beta1 and TGF-beta Type-II receptor mRNA in papillary thyroid carcinoma.
- To explore the potential role of these molecules in the pathogenesis of thyroid cancer.
Main Methods:
- Northern blotting analysis was used to quantify TGF-beta1 and TGF-beta Type-II receptor mRNA levels.
- Expression levels were compared between 14 papillary thyroid carcinomas and adjacent normal thyroid tissues.
- Scanning densitometry, corrected for beta-actin, determined relative mRNA levels.
Main Results:
- Overexpression of TGF-beta1 mRNA was observed in 12 out of 14 papillary thyroid carcinomas compared to normal tissues.
- Reduced TGF-beta Type-II receptor mRNA levels (60.1% of normal) were found in 10 out of 14 papillary thyroid carcinomas.
- No significant correlation was found between mRNA levels and histological characteristics or lymph node metastasis, but a negative correlation existed between TGF-beta Type-II receptor mRNA and tumor size.
Conclusions:
- Papillary thyroid carcinomas frequently exhibit increased TGF-beta1 mRNA and decreased TGF-beta Type-II receptor mRNA.
- The downregulation of TGF-beta Type-II receptor mRNA may contribute to the development of papillary thyroid carcinoma.