Biopolym. Cell. 2019; 35(1):21-29.
Biomedicine
Expression of ITSN2 and TKS5 in different subtypes of breast cancer tumors
1Kropyvko S. V., 1Tsyba L. O., 1Novokhatska O. V., 1Nemesh Y. M., 2Syvak L. A., 2Tarasenko T. Ye., 2Grabovoy A. N., 1Rynditch A. V.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03143
  2. National Cancer Institute
    33/43, Lomonosova Str., Kyiv, Ukraine, 03022

Abstract

Aim. Regardless a great progress in treatment, 15% of breast cancer cases remain lethal. One of the main problems in diagnosis and cure of this cancer type is its high clinical and genetic heterogeneity, and the identification of markers for personalized treatment is still a topical issue. Methods. Collection of clinical material, RNA isolation, and analysis of the ITSN2 and TKS5 isoforms expression using real-time quantitative PCR with fluorescence labeled probes. Results. The reliably reduced expression of ITSN2-S has been found in the HER2/neu-positive tumors with poor prognosis. There was no significant difference in the expression of ITSN2-L and TKS5-L in the analyzed samples. Conclusions. Our study has shown a potential use of the ITSN2 short isoform (ITSN2-S) as a breast cancer prognostic marker.
Keywords: breast cancer, ITSN2, TKS5, mRNA expression analysis.

References

[1] Dai X, Li Y, Bai Z, Tang XQ. Molecular portraits revealing the heterogeneity of breast tumor subtypes defined using immunohistochemistry markers. Sci Rep. 2015;5:14499.
[2] Tang Y, Wang Y, Kiani MF, Wang B. Classification, Treatment Strategy, and Associated Drug Resistance in Breast Cancer. Clin Breast Cancer. 2016;16(5):335-343.
[3] Pourteimoor V, Mohammadi-Yeganeh S, Paryan M. Breast cancer classification and prognostication through diverse systems along with recent emerging findings in this respect; the dawn of new perspectives in the clinical applications. Tumour Biol. 2016;37(11):14479-14499.
[4] Leidy J, Khan A, Kandil D. Basal-like breast cancer: update on clinicopathologic, immunohistochemical, and molecular features. Arch Pathol Lab Med. 2014;138(1):37-43.
[5] Lam SW, Jimenez CR, Boven E. Breast cancer classification by proteomic technologies: current state of knowledge. Cancer Treat Rev. 2014;40(1):129-38.
[6] Eroles P, Bosch A, Pérez-Fidalgo JA, Lluch A. Molecular biology in breast cancer: intrinsic subtypes and signaling pathways. Cancer Treat Rev. 2012;38(6):698-707.
[7] Dai X, Xiang L, Li T, Bai Z. Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes. J Cancer. 2016;7(10):1281-94.
[8] Fusco N, Geyer FC, De Filippo MR, Martelotto LG, Ng CK, Piscuoglio S, Guerini-Rocco E, Schultheis AM, Fuhrmann L, Wang L, Jungbluth AA, Burke KA, Lim RS, Vincent-Salomon A, Bamba M, Moritani S, Badve SS, Ichihara S, Ellis IO, Reis-Filho JS, Weigelt B. Genetic events in the progression of adenoid cystic carcinoma of the breast to high-grade triple-negative breast cancer. Mod Pathol. 2016;29(11):1292-1305.
[9] Schmidt M, Thomssen C, Untch M. Intrinsic Subtypes of Primary Breast Cancer--Gene Expression Analysis. Oncol Res Treat. 2016;39(3):102-10.
[10] Specht K, Harbeck N, Smida J, Annecke K, Reich U, Naehrig J, Langer R, Mages J, Busch R, Kruse E, Klein-Hitpass L, Schmitt M, Kiechle M, Hoefler H. Expression profiling identifies genes that predict recurrence of breast cancer after adjuvant CMF-based chemotherapy. Breast Cancer Res Treat. 2009;118(1):45-56.
[11] Pucharcos C, Casas C, Nadal M, Estivill X, de la Luna S. The human intersectin genes and their spliced variants are differentially expressed. Biochim Biophys Acta. 2001;1521(1-3):1-11.
[12] Adams A, Thorn JM, Yamabhai M, Kay BK, O'Bryan JP. Intersectin, an adaptor protein involved in clathrin-mediated endocytosis, activates mitogenic signaling pathways. J Biol Chem. 2000;275(35):27414-20.
[13] McGavin MK, Badour K, Hardy LA, Kubiseski TJ, Zhang J, Siminovitch KA. The intersectin 2 adaptor links Wiskott Aldrich Syndrome protein (WASp)-mediated actin polymerization to T cell antigen receptor endocytosis. J Exp Med. 2001;194(12):1777-87.
[14] Tsyba L, Nikolaienko O, Dergai O, Dergai M, Novokhatska O, Skrypkina I, Rynditch A. Intersectin multidomain adaptor proteins: regulation of functional diversity. Gene. 2011;473(2):67-75.
[15] Gryaznova T, Kropyvko S, Burdyniuk M, Gubar O, Kryklyva V, Tsyba L, Rynditch A. Intersectin adaptor proteins are associated with actin-regulating protein WIP in invadopodia. Cell Signal. 2015;27(7):1499-508.
[16] Staub E, Groene J, Heinze M, Mennerich D, Roepcke S, Klaman I, Hinzmann B, Castanos-Velez E, Pilarsky C, Mann B, Brümmendorf T, Weber B, Buhr HJ, Rosenthal A. An expression module of WIPF1-coexpressed genes identifies patients with favorable prognosis in three tumor types. J Mol Med (Berl). 2009;87(6):633-44.
[17] Murphy DA, Courtneidge SA. The 'ins' and 'outs' of podosomes and invadopodia: characteristics, formation and function. Nat Rev Mol Cell Biol. 2011;12(7):413-26.
[18] Courtneidge SA. Cell migration and invasion in human disease: the Tks adaptor proteins. Biochem Soc Trans. 2012;40(1):129-32.
[19] Blouw B, Seals DF, Pass I, Diaz B, Courtneidge SA. A role for the podosome/invadopodia scaffold protein Tks5 in tumor growth in vivo. Eur J Cell Biol. 2008;87(8-9):555-67.
[20] Li CM, Chen G, Dayton TL, Kim-Kiselak C, Hoersch S, Whittaker CA, Bronson RT, Beer DG, Winslow MM, Jacks T. Differential Tks5 isoform expression contributes to metastatic invasion of lung adenocarcinoma. Genes Dev. 2013;27(14):1557-67.
[21] Drury S, Anderson H, Dowsett M. Selection of REFERENCE genes for normalization of qRT-PCR data derived from FFPE breast tumors. Diagn Mol Pathol. 2009;18(2):103-7.
[22] Lyng MB, Laenkholm AV, Pallisgaard N, Ditzel HJ. Identification of genes for normalization of real-time RT-PCR data in breast carcinomas. BMC Cancer. 2008;8:20.
[23] Radonić A, Thulke S, Mackay IM, Landt O, Siegert W, Nitsche A. Guideline to reference gene selection for quantitative real-time PCR. Biochem Biophys Res Commun. 2004;313(4):856-62.