Association between transforming growth factor-β1 expression and the clinical features of triple negative breast cancer

Abstract

Abstract. The aim of the present study was to investigate the association between the expression levels of transforming growth factor-β1 (TGF-β1) and the clinical pathological characteristics and prognosis of triple negative breast cancer (TNBC) through study of TNBC patient tissue samples. The biological effects of TGF-β1 on TNBC cells and the potential signal transduction pathway are additoinally investigated. Immunohistochemistry was utilized to investigate expression changes of the positive rate of TGF-β1 in the TNBC, compared with the non-TNBC group, to explain the association between TGF-β1 and clinical pathological characteristics and prognosis. MDA-MB-231 cells were treated with TGF-β1 and subsequently the invasion and migration abilities, and the expression of proteins in certain signaling pathways were assessed before and after the treatment. Positive expression of TGF-β1 was observed in 52.5% of TNBC tissue samples, which was higher than that observed in non-TNBC group (27.5%). High levels of TGF-β1 expression were not significantly associated age, menopausal status, family history of cancer or tumor size; however, tumor histological grade and axillary lymph node metastasis were significantly associated (P<0.05). In addition, when the TGF-β1 expression levels are higher, the 5-year disease-free survival rate is lower. TGF-β1 expression promoted the invasion and migration of MDA-MB-231 cells, and the expression of Smad2 protein and P38 protein was increased, indicating that Smad2 protein and the P38 signaling pathway may serve an important role in TNBC.

miR-145 inhibits proliferation and migration of breast cancer cells by directly or indirectly regulating TGF-β1 expression

“…From previous studies we know that TGF-β1 may play an important role in growth and metastasis of breast cancer cells (11). During tumor development, tumor cells secrete large amounts of active TGF-β1 which may promote tumor invasion and metastasis (30). In this study, we demonstrated TGF-β1 as a factor mediating the effect of miR-145.…”

Clinically Translatable Approaches of Inhibiting TGF-β to Target Cancer Stem Cells in TNBC

“…Upon assessment, it was found that there was no significant correlation between TGF-β1 expression and age, menopause, family history, or tumor size. However, there was a significant association between histological grade (grade III samples; 34 cases in TGF-β1 high samples versus 4 cases in TGF-β1 low samples) and positive axillary lymph node tumor migration (33 cases for TGF-β1 high samples versus 16 cases in TGF-β1 low samples) [35]. Additionally, the 5-year disease-free survival assessment of the patients revealed a substantial decrease in patients with high TGF-β1 expression versus those that did not [35].…”

“…However, there was a significant association between histological grade (grade III samples; 34 cases in TGF-β1 high samples versus 4 cases in TGF-β1 low samples) and positive axillary lymph node tumor migration (33 cases for TGF-β1 high samples versus 16 cases in TGF-β1 low samples) [35]. Additionally, the 5-year disease-free survival assessment of the patients revealed a substantial decrease in patients with high TGF-β1 expression versus those that did not [35]. The authors assessed the effects of TGF-β1 exposure using an in vitro TNBC model and it was found that both cellular invasion and metastasis were enhanced once TGF-β1 expression was increased [35].…”

“…Ding et al assessed the correlation between TGFβ signaling and adverse pathological characteristics in TNBC. Amongst the patient samples, 52.5% of TNBC cases were found to express high levels of TGF-β1 [35]. Upon assessment, it was found that there was no significant correlation between TGF-β1 expression and age, menopause, family history, or tumor size.…”

TIMAP Upregulation Correlates Negatively with Survival in HER2- Negative Subtypes of Breast Cancer

“…This result could not be directly related to the lack of expression of ER, PR, or HER2, as the non-triple negative subtypes express at least one of these proteins and show similar expression of TIMAP. However, since TIMAP has been shown to be downregulated by TGFβ1 (Cao et al, 2002;Yang et al, 2017) and that TGFβ1 is significantly upregulated in triple negative breast cancer as opposed to non-triple negative subtypes (Ding et al, 2016), it is plausible to suggest that the reduced level of TIMAP protein observed in the triple negative subtype here could be explained by presumably upregulated TGFβ1 expression. Nevertheless, future analyses are required to examine this possibility.…”