Trefoil factors peptide-3 is associated with residual invasive breast carcinoma following neoadjuvant chemotherapy

Abstract

BackgroundBreast carcinoma is the commonest cancer among UAE population and the most common cancer among females. Examination of the 5′ promoter regions of trefoil factor 3 (TFF3) gene has identified putative estrogen and progesterone receptor–DNA binding domains as direct response elements to estrogen and progesterone that are linked to breast functions or steroid regulation. The study was designed to determine the role of TFF3 in breast cancer chemoresistance with the aim of establishing TFF3 expression as a biomarker for drug resistance.MethodsIn total, 133 cases of breast carcinoma treated with neo-adjuvant therapy were collected. Tissue samples from pre-neoadjuvant therapy as well as tissues from post-neo-adjuvant therapy of those cases were collected and stained with immunohistochemistry for TFF3, Bcl2, BAX, cleaved caspase-3, AKT-1, NF kappa B and Ki-67.ResultsThere was increased expression of TFF3 in residual invasive carcinoma cells. There was a significant correlation between the expression of TFF3 in breast carcinoma cells and response to neoadjuvant chemotherapy (p = 0.0165). There was significant co-expression of TFF3 with AKT1 (p = 0.0365), BCl2 (p = 0.0152), and NF Kappa-B (p = 0.0243) in breast carcinoma cases with residual carcinoma following neoadjuvant therapy which support the role of TFF3 in chemoresistance.ConclusionThe expression of TFF3 is significantly associated with residual breast carcinoma following neoadjuvant chemotherapy suggesting its expression is associated with increased resistance to chemotherapy. This is supported by its co-expression with antiapoptotic proteins; BCl2, AKT1 and NF Kappa-B in residual breast carcinoma cells and very low proliferating index and apoptotic bodies in residual tumors.Electronic supplementary materialThe online version of this article (10.1186/s12885-019-5316-y) contains supplementary material, which is available to authorized users.

Inhibition of TFF3 Enhances Sensitivity—and Overcomes Acquired Resistance—to Doxorubicin in Estrogen Receptor-Positive Mammary Carcinoma

“…Herein, increased AKT activity together with the elevated TFF3 expression were observed in response to doxorubicin treatment and in acquired doxorubicin resistant ER+MC. This is consistent with the observation in neoadjuvant chemotherapy resistant MC where TFF3 expression and phosphorylated-AKT1 were co-localized [54]. Considering the pro-survival properties of TFF3 [12,13,14,15], as well as its downstream activation of AKT [39,40,46,59], it can be concluded that TFF3 promotes the activation of AKT leading to the inhibition of doxorubicin-induced apoptosis.…”

“…In addition to TFF3 reduction of doxorubicin sensitivity, TFF3 has been reported as a biomarker of poor response to various chemotherapeutic agents [31]. A recent study has demonstrated that high TFF3 expression is associated with residual disease after neoadjuvant chemotherapy of invasive ductal carcinoma whereas low TFF3 expression is associated with a complete pathological response [54]. Consistently in our study, elevated levels of TFF3 are observed in ER+MC with acquired doxorubicin resistance, whilst the depletion or AMPC-mediated inhibition of TFF3 partially re-sensitized the resistant cells to doxorubicin-induced cytotoxicity and apoptosis.…”

Extracellular production of recombinant sus scrofa trefoil factor 3 by Brevibacillus choshinensis

“…The interaction between TFF3 and mucins has also been reported to protect intestinal epithelia from injuries, maintaining mucosal barrier function (26). Furthermore, mitogenic effects of TFF3 have been identified in vitro in primary cell culture, and TFF3 has been demonstrated to inhibit apoptosis, induce cellular invasion, act as an inflammatory modulator and exhibit pro-angiogenic activity (27)(28)(29)(30)(31)(32). A protective or healing effect of TFF3 has also been reported in a series of experiments, such as cells in vitro, mice, rats and human (12)(13)(14)(15)(16)(17).…”

Comparison of Serum Trefoil Factor-3 to Endoscopy in Diagnosing Helicobacter Pylori Associated Gastric Ulcer

“…(Aamann et al, 2014) An emerging role for Tf3 has been documented in oncogenic transformation, and metastatic extension of solid tumors, such as prostate (Abou-Ouf et al, 2019) and breast cancers. (Al-Salam et al, 2019) The suitability of blood-based biomarkers in diagnosing gastric metaplasia was tackled in several studies. For instance, study revealed a close correlation between serum pepsinogen and upper gastrointestinal endoscopic findings in seropositive and seronegative H.pylori subjects.…”