Inhibition of ErbB-2 induces TFF3 downregulation in breast cancer cell lines

Abstract

ErbB-2 gene plays an important role in carcinoma formation whose overexpression was observed in many types of tumors, including breast cancer. Dysregulation of Trefoil factor 3 (TFF3), which is thought to function in the development and progression of breast cancer, was found to be upregulated in ErbB2-overexpressing breast cancers and cells. However, a putative interaction between ErbB-2 and TFF3 in breast cancer remains unknown. To determine whether TFF3 has an important role in breast tumor, its levels were measured by immunohistochemistry in 130 cases of breast infiltrating duct carcinoma and 30 cases of normal breast tissue with a specific monoclonal antibody raised against human TFF3. Patients who were positive for ErbB-2 also had high expression levels of TFF3 (p < 0.05). Also, after infecting the SK-BR-3 cells with lentivirus-mediated ErbB2-specific shRNA (Lenti-ShERBB2), we detected the expressions of ErbB-2 and TFF3 by real-time polymerase chain reaction and Western blotting, respectively. Compared with the control groups, ErbB-2 mRNA expression was decreased in the Lenti-ShERBB2 infection group, and Western blotting indicated a concordant ErbB-2 protein reduction. On the other hand, TFF3 expression at both mRNA and protein levels was significantly downregulated by ErbB-2 silencing in SK-BR-3. These findings are a proof of the foundation for a certain relationships of ErbB-2 and TFF3, which may serve as novel therapeutic markers of ErbB2-overexpressing breast cancers in the future.

Release of HER2 repression of trefoil factor 3 (TFF3) expression mediates trastuzumab resistance in HER2+/ER+ mammary carcinoma

“…Our current findings are consistent with these observations in that HER2 transcriptionally represses TFF3, while trastuzumab inhibition of HER2 releases the transcriptional repression on TFF3 in HER2+/ER+ breast cancer cells. In contrast to our findings of trastuzumab-stimulated upregulation of TFF3 in BT474 cells, Yue et al observed that the silencing of HER2 induced TFF3 downregulation in HER2+/ER− SKBR3 cells [ 65 ]. This discrepancy may be attributed to two reasons.…”

Overexpression of trefoil factor 1 and trefoil factor 3 in primary extramammary Paget's disease and implication of a novel therapeutic target

“…A relationship of HER-2 and TFF3 has been confirmed in a breast cancer study, which identified TFF3 expression to be strictly associated with HER2 amplification in SK-BR-3 cells. 2 A meta-analysis study revealed that HER2 overexpression/amplification is one of the fundamental pathogenetic pathways in patients affected by EMPD. The TFFs could be applied as therapeutic targets based on their role in the biological processes.…”