Role of TGF-β1 and its Receptors in Breast Carcinogenesis： Evaluation of Gene Expression Pattems and Clinical Implications

OBJECTIVE Transforming growth factor β1 （TGF-β1） is a multifunc- tional cytokine that may play an important role in tumor development and progression. METHODS We evaluated gene expression patterns of TGF-β1 and its receptors transforming growth factor β type Ⅰ receptor （TβR- Ⅰ ） and transforming growth factor β type Ⅱ receptor （TβR- Ⅱ ）] in tumor tissue from patients with breast cancer or with benign breast diseases （BBD） and adjacent normal tissue from the patients with breast cancer. Included in the study were 527 breast cancer patients and 213 BBD patients who participated in the Shanghai Breast Cancer Study. RESULTS The expression levels of the TGF-β1, TβR- Ⅰ and TβR-Ⅱ genes in breast tissue were quantified using real-time PCR. TIER- Ⅱ expression in cancer tissue was decreased by over 50% as compared to either adjacent normal tissue from the same patients or benign tumor tissue from BBD patients （p〈0.001）. TGF-β1 expression was lower by approximately 20% in cancer tissue compared to adjacent normal tissue （p=0.14） or to benign tumor tissue （p=0.002）. Although TβR-Ⅰ expression was also reduced in cancer tissue compared to adjacent normal tissue, or benign tumor tissue, the magnitude of the reduction was less apparent than that for TβR- Ⅱ. Compared to patients with the lowest tertile value for TβR- Ⅱ, patients with median tertile value for TβR- Ⅱ had more favorable overall survival （HR 0.47, 95% CI 0.27-0.85） and disease-free survival （HR 0.65, 95% CI 0.39-1.06）. No apparent associations, however, were observed between TGF-β1 or TβR- Ⅰ expression and overall or disease-free survival. CONCLUSION The results from this study support the hypothesis that a decreased level of TβR-Ⅱ gene expression, and thus reduced TGF-β1 sensitivity, is related to breast tumor progression.

Role of TGF-β1 and its receptors in breast carcinogenesis: Evaluation of gene expression patterns and clinical implications

Objective Transforming growth factor β1 (TGF-β1) is a multifunctional cytokine that may play an important role in tumor development and progression. Methods We evaluated gene expression patterns of TGF-β1 and its receptors transforming growth factor β type I receptor (TβR-I) and transforming growth factor β type II receptor (TβR-II)] in tumor tissue from patients with breast cancer or with benign breast diseases (BBD) and adjacent normal tissue from the patients with breast cancer. Included in the study were 527 breast cancer patients and 213 BBD patients who participated in the Shanghai Breast Cancer Study. Results The expression levels of the TGF-β1, TβR-I and TβR-II genes in breast tissue were quantified using real-time PCR. TβR-II expression in cancer tissue was decreased by over 50% as compared to either adjacent normal tissue from the same patients or benign tumor tissue from BBD patients (p<0.001). TGF-β1 expression was lower by approximately 20% in cancer tissue compared to adjacent normal tissue (p=0.14) or to benign tumor tissue (p=0.002). Although TβR-I expression was also reduced in cancer tissue compared to adjacent normal tissue, or benign tumor tissue, the magnitude of the reduction was less apparent than that for TβR-II. Compared to patients with the lowest tertile value for TβR-II, patients with median tertile value for TβR-II had more favorable overall survival (HR 0.47, 95% CI 0.27–0.85) and disease-free survival (HR 0.65, 95% CI 0.39–1.06). No apparent associations, however, were observed between TGF-β1 or TβR-I expression and overall or disease-free survival. Conclusion The results from this study support the hypothesis that a decreased level of TβR-II gene expression, and thus reduced TGF-β1 sensitivity, is related to breast tumor progression. This work was supported by a grant from the Science and Technology Commission of Shanghai Municipality (05JC14086), NIH grants RO1 CA64277 and RO1 CA90899 from the National Cancer Institute, USA.