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BMC Cancer

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Open Access 01-12-2019 | Cytostatic Therapy | Research article

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

Authors: Suhail Al-Salam, Manjusha Sudhadevi, Aktham Awwad, Mohamed Al Bashir

Published in: BMC Cancer | Issue 1/2019

Abstract

Background

Breast 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.

Methods

In 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.

Results

There 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.

Conclusion

The 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.

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Yusra Elobaid, Tar-Ching Aw, Jennifer N.W. Lim, Saima Hamid, Michal Grivna Breast cancer presentation delays among Arab and national women in the UAE: a qualitative study. SSM Popul Health 2016 Dec; 2: 155–163.

Cancer Incidence report 1998-2001. United Arab Emirates National Cancer Registry, Department of Disease Control, Ministry of health, UAE, 2003.

Howell A, Anderson AS, Clarke RB, Duffy SW, Gareth Evans D, Garcia-Closas M, Gescher AJ, Key TJ, Saxton JM, Harvie MN. Risk determination and prevention of breast cancer. Breast Cancer Res. 2014;16:446.PubMedPubMedCentralCrossRef

Hoffmann W, Jagla W, Wiede A. Molecular medicine of TFF-peptides: from gut to brain. Histol Histopathol. 2001 Jan;16(1):319–34.PubMed

Jakowlew SB, Breathnach R, Jeltsch JM, Masiakowski P, Chambon P. Sequence of the pS2 mRNA induced by estrogen in the human breast cancer cell line MCF-7. Nucleic Acids Res. 1984;12:2861–78.PubMedPubMedCentralCrossRef

Jorgensen KH, Thim L, Jacobsen HE. Pancreatic spasmolytic polypeptide (PSP). I. Preparation and initial chemical characterization of a new polypeptide from porcine pancreas. Regul. Pept. 1982;34:207–19.CrossRef

Schmitt H, Wundrack I, Beck S, Gott P, Welter C, Shizuya H, et al. A third P-domain peptide gene (TFF3), human intestinal trefoil factor, maps to 21q22.3as. Cytogenet. Cell Genet. 1996;72:299–302.CrossRef

Ahmed AR, Griffiths AB, Tilby MT, Westley BR, May FE. TFF3 is a normal breast epithelial protein and is associated with differentiated phenotype in early breast cancer but predisposes to invasion and metastasis in advanced disease. Am J Pathol. 2012;180(3):904–16.PubMedCrossRef

Ishibashi Y, Ohtsu H, Ikemura M, Kikuchi Y, Niwa T, Nishioka K, Uchida Y, Miura H, Aikou S, Gunji T, Matsuhashi N, Ohmoto Y, Sasaki T, Seto Y, Ogawa T, Tada K, Nomura S. Serum TFF1 and TFF3 but not TFF2 are higher in women with breast cancer than in women without breast cancer. Sci Rep. 2017 Jul 7;7(1):4846.PubMedPubMedCentralCrossRef

10.

Borthwick JM, Charnock-Jones DS, Tom BD, Hull ML, Teirney R, Phillips SC, et al. Determination of the transcript profile of human endometrium. Mol Hum Reprod. 2003;9:19–33.PubMedCrossRef

11.

Chevallier B, Roche H, Olivier JP, Chollet P, Hurteloup P. Inflammatory breast cancer. Pilot study of intensive induction chemotherapy (FEC-HD) results in a high histologic response rate. Am J Clin Oncol. 1993 Jun;16(3):223–8.PubMedCrossRef

12.

Gonzalez-Angulo AM, Morales-Vasquez F, Hortobagyi GN. Overview of resistance to systemic therapy in patients with breast cancer. Adv Exp Med Biol. 2007;608:1–22.PubMedCrossRef

13.

Geretto M, Pulliero A, Rosano C, Zhabayeva D, Bersimbaev R, Izzotti A. Resistance to cancer chemotherapeutic drugs is determined by pivotal microRNA regulators. Am J Cancer Res 2017 Jun 1;7(6):1350–1371. eCollection 2017.

14.

Kerbel RS, Kobayashi H, Graham CH. Intrinsic or acquired drug resistance and metastasis: are they linked phenotypes? J Cell Biochem. 1994;56:37–47.PubMedCrossRef

15.

Longley DB, Johnston PG. Molecular mechanisms of drug resistance. J Pathol. 2005;205:275–92.PubMedCrossRef

16.

Al-Salam S. Role of trefoil factor 3 in breast carcinoma chemoresistance. Oral presentation abstract. 29^Th European congress of pathology. Virchows Arch. 2017;471(Suppl 1):S23.

17.

Taupin DR, Kinoshita K, Podolsky DK. Intestinal trefoil factor confers colonic epithelial resistance to apoptosis. Proc Natl Acad Sci U S A 2000 18;97(2):799–804.

18.

Taupin D, Wu DC, Jeon WK, Devaney K, Wang TC, Podolsky DKJ. The trefoil gene family are coordinately expressed immediate-early genes: EGF receptor- and MAP kinase-dependent interregulation. Clin Invest. 1999;103:R31–8.CrossRef

19.

Durual S, Blanchard C, Estienne M, Jacquier MF, Cuber JC, Perrot V, Laboisse C, Cuber JC. Expression of human TFF3 in relation to growth of HT-29 cell subpopulations: involvement of PI3-K but not STAT6. Differentiation. 2005;73(1):36–44.PubMedCrossRef

20.

You ML, Chen YJ, Chong QY, Wu MM, Pandey V, Chen RM, Liu L, Ma L, Wu ZS, Zhu T, Lobie PE. Trefoil factor 3 mediation of oncogenicity and chemoresistance in hepatocellular carcinoma is AKT-BCL-2 dependent Oncotarget. Jun 13. 2017;8(24):39323–44.

21.

Hanisch C, Sharbati J, Kutz-Lohroff B, Huber O, Einspanier R, Sharbati S. TFF3-dependent resistance of human colorectal adenocarcinoma cells HT-29/B6 to apoptosis is mediated by miR-491-5p regulation of lncRNA PRINS. Cell Death Discov. 2017 Jan 30;3:16106.PubMedPubMedCentralCrossRef

22.

Sun Z, Liu H, Yang Z, Shao D, Zhang W, Ren Y, Sun B, Lin J, Xu M, Nie S. Intestinal trefoil factor activates the PI3K/Akt signaling pathway to protect gastric mucosal epithelium from damage. Int J Oncol. 2014 Sep;45(3):1123–32.PubMedCrossRef

23.

Kinoshita T, Taupin DR, Itoh H, Podolsky DK. Distinct pathways of cell migration and antiapoptotic response to epithelial injury: structure-function analysis of human intestinal trefoil factor. Mol Cell Biol. 2000;20:4680–90.PubMedPubMedCentralCrossRef

24.

Casado E, Garcia VM, Sánchez JJ, Gómez Del Pulgar MT, Feliu J, Maurel J, Castelo B, Moreno Rubio J, López RA, García-Cabezas MÁ, Burgos E, de Castro J, Belda-Iniesta C, López-Gómez M, Gómez-Raposo C, Zambrana F, Sereno M, Fernández-Martos C, Vázquez P, Lacal JC, González-Barón M, Cejas P. Upregulation of trefoil factor 3 (TFF3) after rectal cancer chemoradiotherapy is an adverse prognostic factor and a potential therapeutic target. Int J Radiat Oncol Biol Phys. 2012;84(5):1151–8.PubMedCrossRef

25.

Zhu YQ, Tan XD. TFF3 modulates NF-{ Kappa} B and a novel negative regulatory molecule of NF-{ Kappa} B in intestinal epithelial cells via a mechanism distinct from TNF-{alpha}. Am J Physiol Cell Physiol. 2005;289(5):C1085–93.PubMedPubMedCentralCrossRef

26.

Li Q, Yang G, Feng M, Zheng S, Cao Z, Qiu J, You L, Zheng L, Hu Y, Zhang T, Zhao Y. NF-κB in pancreatic cancer: Its key role in chemoresistance. Cancer Lett. 2018 May 1;421:127–34.PubMedCrossRef

27.

Wang H, Cai J, Du S, Guo Z, Xin B, Wang J, Wei W, Shen X. Fractalkine/CX3CR1 induces apoptosis resistance and proliferation through the activation of the AKT/NF-κB cascade in pancreatic cancer cells. Cell Biochem Funct. 2017 Aug;35(6):315–26. https://doi.org/10.1002/cbf.3278.PubMedCrossRef

28.

Chen YH, Lu Y, De Plaen IG, Wang LY, Tan XD. Transcription factor NF- KappaB signals antianoikic function of trefoil factor 3 on intestinal epithelial cells. Biochem Biophys Res Commun. 2000;274(3):576–82.PubMedCrossRef

Title: Trefoil factors peptide-3 is associated with residual invasive breast carcinoma following neoadjuvant chemotherapy
Authors: Suhail Al-Salam
Manjusha Sudhadevi
Aktham Awwad
Mohamed Al Bashir
Publication date: 01-12-2019
Publisher: BioMed Central
Keyword: Cytostatic Therapy
Published in: BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-019-5316-y

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