Neural Transdifferentiation: MAPTau Gene Expression in Breast Cancer Cells

  • Lara-Padilla, E (Laboratory of Molecular Oncology and Oxidative Stress, ESM, IPN) ;
  • Miliar-Garcia, A (Laboratory of Molecular Biology, ESM, IPN) ;
  • Gomez-Lopez, M (Laboratory of Molecular Biology, ESM, IPN) ;
  • Romero-Morelos, P (Laboratory of Genomic Oncology, Medical Research Unit in Oncological Diseases, Centro Medico Nacional Siglo XXI, IMSS) ;
  • Bazan-Mendez, CI (Laboratory of Cellular Biology, CINVESTAV) ;
  • Alfaro-Rodriguez, A (Division of Neuroscience, INR, SSA) ;
  • Anaya-Ruiz, M (Laboratory of Cellular Biology CIBIOR, IMSS) ;
  • Callender, K (Cardio-Neuropthalmological and Transplant Center, Ministry of Public Health) ;
  • Carlos, A (Electron Microscopy Laboratory, INR, SSA) ;
  • Bandala, C (Division of Neuroscience, INR, SSA)
  • Published : 2016.06.01


Background: In tumor cells, aberrant differentiation programs have been described. Several neuronal proteins have been found associated with morphological neuronal-glial changes in breast cancer (BCa). These neuronal proteins have been related to mechanisms that are involved in carcinogenesis; however, this regulation is not well understood. Microtubule-associated protein-tau (MAP-Tau) has been describing in BCa but not its variants. This finding could partly explain the neuronal-glial morphology of BCa cells. Our aim was to determine mRNA expression of MAP-tau variants 2, 4 and 6 in breast cancer cell lines. Materials and Methods: Cultured cell lines MCF-10A, MDA-MB-231, SKBR3 and T47D were observed under phase-contrast microscopy for neural morphology and analyzed for gene expression of MAP-Tau transcript variants 2, 4 and 6 by real-time PCR. Results: Regarding morphology like neural/glial cells, T47D line shown more cells with these features than MDA-MB-231 and SKBR. In another hand, we found much greater mRNA expression of MAP-Tau transcript variants 2, and to a lesser extent 4 and 6, in T47D cells than the other lines. In conclusion, regulation of MAP-Tau could bring about changes in cytoskeleton, cell morphology and motility; these findings cast further light on neuronal transdifferentiation in BCa.


  1. Ahmad M, Attoub S, Singh MN, Martin FL, El-Agnaf OM (2007). Gamma-synuclein and the progression of cancer. FASEB J, 21, 3419-30.
  2. Anaya-Ruiz M, Vallejo-Ruiz V, Flores-Mendoza L, Perez-Santos M (2014). Female breast cancer incidence and mortality in Mexico, 2000-2010. Asian Pac J Cancer Prev, 15, 1477-9.
  3. Bandala C, Miliar-García A, Mejía-Barradas CM, et al (2012) Synaptic vesicle protein 2 (SV2) isoforms. Asian Pac J Cancer Prev, 13, 5063-7.
  4. Barneda-Zahonero B, Roman-Gonzalez L, Collazo O, Mahmoudi T, Parra M (2012). Epigenetic regulation of B lymphocyte differentiation, transdifferentiation, and reprogramming. Comp Funct Genomics, 2012, 564381.
  5. Barrachina M, Ferrer I (2009). DNA methylation of Alzheimer disease and tauopathy-related genes in postmortem brain. J J Neuropathol Exp Neurol, 68, 880-1.
  6. Bassett T, Harpur B, Poon HY, Kuo KH, Lee CH (2008). Effective stimulation of growth in MCF-7 human breast cancer cells by inhibition of syntaxin18 by external guide sequence and ribonuclease P. Cancer Lett, 272, 167-75.
  7. Battula VL, Shi Y, Evans KW, et al (2012). Ganglioside GD2 identifies breast cancer stem cells and promotes tumorigenesis. J Clin Invest, 122, 2066-8.
  8. Bauer JA, Chakravarthy AB, Rosenbluth JM, et al (2012). Identification of markers of taxane sensitivity using proteomic and genomic analyses of breast tumors from patients receiving neoadjuvant paclitaxel and radiation. Clin Cancer Res, 16, 681-0.
  9. Bengtsson T, Jaconi ME, Gustafson M, et al (1993). Actin dynamics in human neutrophils during adhesion and phagocytosis is controlled by changes in intracellular free calcium. Eur J Cell Biol, 62, 49-8.
  10. Chapin SJ, Bulinski JC (1992). Microtubule stabilization by assembly-promoting microtubule-associated proteins: a repeat performance. Cell Motil Cytoskeleton, 23, 236-3.
  11. Cheng Y, Gaughan J, Midic U et al (2013). Systems genetics implicates cytoskeletal genes in oocyte control of cloned embryo quality. Genetics, 193, 877-6.
  12. Cho KJ, Trzaska KA, Greco SJ, et al (2005). Neurons derived from human mesenchymal stem cells show synaptic transmission and can be induced to produce the neurotransmitter substance P by interleukin-1 alpha. Stem Cells, 23, 383-1.
  13. Endo Y, Toyama T, Takahashi S et al (2013). miR-1290 and its potential targets are associated with characteristics of estrogen receptor alpha-positive breast cancer. Endocr Relat Cancer, 20, 91-2.
  14. Goedert M, Wischik CM, Crowther RA, Walker JE, Klug A (1988). Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau. Proc Natl Acad Sci USA, 85, 4051-5.
  15. Goedert M, Spillantini MG, Jakes R, Rutherford D, Crowther RA (1989). Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer’s disease. Neuron, 3, 519-26.
  16. Guo J, Shou C, Meng L, et al (2007). Neuronal protein synuclein gamma predicts poor clinical outcome in breast cancer. Int J Cancer, 121, 1296-305.
  17. Harada A, Oguchi K, Okabe S (1994). Altered microtubule organization in small-calibre axons of mice lacking tau protein. Nature, 369, 488-1.
  18. Honig A, Gehrmann M, Kranke P, et al. (2014). Microtubuleassociated protein tau correlates with estrogen receptor status but not with in vitro paclitaxel sensitivity in primary breast cancer. Eur J Gynaecol Oncol, 35, 503-7.
  19. Ikeda H, Taira N, Hara F et al. (2010). The estrogen receptor influences microtubule-associated protein tau (MAPT) expression and the selective estrogen receptor inhibitor fulvestrant downregulates MAPT and increases the sensitivity to taxane in breast cancer cells. Breast Cancer Res, 12, 43.
  20. Kanojia D, Morshed RA, Zhang L, et al (2015). ${\beta}III$-tubulin regulates breast cancer metastases to the brain. Mol Cancer Ther, 14, 1152-61.
  21. Kolacinska A, Fendler W, Szemraj J et al (2012). Gene expression and pathologic response to neoadjuvant chemotherapy in breast cancer. Mol Biol Rep, 39, 7435-1.
  22. Kotoula V, Kalogeras KT, Kouvatseas G et al (2013). Sample parameters affecting the clinical relevance of RNA biomarkers in translational breast cancer research. Virchows Arch, 462, 141-4.
  23. Ksiazkiewicz M, Markiewicz A, Zaczek AJ (2012). Epithelialmesenchymal transition: a hallmark in metastasis formation linking circulating tumor cells and cancer stem cells. Pathobiol, 79, 195-8.
  24. Leon-Hernandez SR, Padilla EL, Algara AC, et al (2014). Relation of alcohol/tobacco use with metastasis, hormonal (estrogen and progesterone) receptor status and c-erbB2 protein in mammary ductal carcinoma. Asian Pac J Cancer Prev, 15, 5709-14.
  25. Leontovich AA, Zhang S, Quatraro C et al (2012). Raf-1 oncogenic signaling is linked to activation of mesenchymal to epithelial transition pathway in metastatic breast cancer cells. Int J Oncol, 40, 1858-4.
  26. Lim RW, Halpain S (2000). Regulated association of microtubule-associated protein 2 (MAP2) with Src and Grb2: evidence for MAP2 as a scaffolding protein. J Biol Chem, 275, 20578-7.
  27. Liu Q, Guan L, Huang B, et al (2011). Adult peripheral blood mononuclear cells transdifferentiate in vitro and integrate into the retina in vivo. Cell Biol Int, 35, 631-8.
  28. McPherson K, Steel CM, Dixon JM (2000). ABC of breast diseases. Breast cancer-epidemiology, risk factors, and genetics. BMJ, 321, 624-8.
  29. Mietelska-Porowska A, Wasik U, Goras M, Filipek A, Niewiadomska G (2014). Tau protein modifications and interactions: their role in function and dysfunction. Int J Mol Sci, 15, 4671-3.
  30. Moelans CB, de Wegers RA, Monsuurs HN, Maess AH, van Diest PJ (2011). Molecular differences between ductal carcinoma in situ and adjacent invasive breast carcinoma: a multiplex ligation-dependent probe amplification study. Cell Oncol, 34, 475-2.
  31. Palafox M, Ferrer I, Pellegrini P et al (2012). RANK induces epithelial-mesenchymal transition and stemness in human mammary epithelial cells and promotes tumorigenesis and metastasis. Cancer Res, 72, 2879-8.
  32. Paris AJ, Snapir Z, Christopherson CD et al (2011). A polymorphism that delays fibrosis in hepatitis C promotes alternative splicing of AZIN1, reducing fibrogenesis. Hepatol, 54, 2198-7.
  33. Pentheroudakis G, Batistatou A, Kalogeras KT et al (2011). Prognostic utility of beta-tubulin isotype III and correlations with other molecular and clinicopathological variables in patients with early breast cancer: a translational Hellenic Cooperative Oncology Group (HeCOG) study. Breast Cancer Res Treat, 127, 179-3.
  34. Perez-Santos JL, Anaya-Ruiz M (2013). Mexican breast cancer research output, 2003-2012. Asian Pac J Cancer Prev, 14, 5921-3.
  35. Ray B, Chauhan NB, Lahiri DK (2011). The "aged garlic extract:" (AGE) and one of its active ingredients S-allyl-L-cysteine (SAC) as potential preventive and therapeutic agents for Alzheimer's disease (AD). Curr Med Chem, 18, 3306-3.
  36. Rody A, Karn T, Gätje R et al (2007). Gene expression profiling of breast cancer patients treated with docetaxel, doxorubicin, and cyclophosphamide within the GEPARTRIO trial: HER- 2, but not topoisomerase II alpha and microtubule-associated protein tau, is highly predictive of tumor response. Breast, 16, 86-3.
  37. Sadeqzadeh E, Rahbarizadeh F, Ahmadvand D, et al (2011). Combined MUC1-specific nanobody-tagged PEGpolyethylenimine polyplex targeting and transcriptional targeting of tBid transgene for directed killing of MUC1 over-expressing tumour cells. J Control Release, 156, 85-91.
  38. Sadi AM, Wang DY, Youngson BJ et al (2011). Clinical relevance of DNA microarray analyses using archival formalin-fixed paraffin-embedded breast cancer specimens. BMC Cancer, 11, 1-3.
  39. Sariego J (2010). Breast cancer in the young patient. Am Surg, 76, 1397-0.
  40. Seeger MA, Rice SE (2010). Microtubule-associated protein-like binding of the kinesin-1 tail to microtubules. J Biol Chem, 285, 8155-62.
  41. Shin RW, Iwaki T, Kitamoto T, Tateishi J (1991). Hydrated autoclave pretreatment enhances tau immunoreactivity in formalin-fixed normal and Alzheimer’s disease brain tissues. Lab Invest, 64, 693-702.
  42. Soto-Perez-de-Celis E, Chavarri-Guerra Y (2016). National and regional breast cancer incidence and mortality trends in Mexico 2001-2011: Analysis of a population-based database. Cancer Epidemiol, 41, 24-33.
  43. Sreenath AS, Kumar KR, Reddy GV, et al (2005). Evidence for the association of synaptotagmin with glutathione S-transferases: implications for a novel function in human breast cancer. Clin Biochem, 38, 436-43.
  44. Williams KC, McNeilly RE, Coppolino MG (2014). SNAP23, Syntaxin4, and vesicle-associated membrane protein 7 (VAMP7) mediate trafficking of membrane type 1-matrix metalloproteinase (MT1-MMP) during invadopodium formation and tumor cell invasion. Mol Biol Cell, 25, 2061-70.
  45. Zhang H, Kouadio A, Cartledge D, Godwin AK (2011). Role of gamma-synuclein in microtubule regulation. Exp Cell Res, 317, 1330-9.
  46. Zhang Q, Fan H, Shen J, Hoffman RM, Xing HR (2010). Human breast cancer cell lines co-express neuronal, epithelial, and melanocytic differentiation markers in vitro and in vivo. PLoS One, 5, 9712.
  47. Zhou J, Qian S, Li H et al (2015). Predictive value of microtubule-associated protein Tau in patients with recurrent and metastatic breast cancer treated with taxane-containing palliative chemotherapy. Tumour Biol, 36, 3941-7.