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Immunofluorescent analyses of tumor marker beta-III tubuilin expression in tumor and ajacent normal lung tissue derived from patients with non-small cell lung cancer

https://doi.org/ 10.17650/1726-9784-2016-15-2-16-18

Abstract

Background. Class III beta-tubulin (TUBB3) is one of the eight beta tubulin isotypes identified in human. It is constitutively expressed in brain and testis but not in lung tissue. TUBB3 is also known to appear in solid tumors, in particular in non-small cell lung cancer (NSCLC), and it is often associated with poor prognosis and resistance to taxanes and Vinka alkaloids. Objective: We have suggested that TUBB3 expression may cover not only the primary tumor but also a wide adjacent area of morphologically normal lung tissue. To check the hypothesis we have measured TUBB3 expression both in the non-small cell lung carcinoma (NSCLC) and remote lung tissue derived from the same lung. 60surgical biopsy specimens of NSCLC and morphologically normal lung tissue of 30patients were investigated. Materials and methods. Biopsy specimens were converted to suspension, fixed in 4 % formaldehyde and analyzed by flow cytometry using monoclonal antibodies to TUBB3. The method was developed in the laboratory of medicinal chemistry research Institute of experimental diagnostics and therapy of tumors (N.N. Blokhin Russian Cancer Research Center) and patented. Results. Fraction of TUBB3-positive cells in the group of adjacent lung tissue specimens was lower compared to NSCLC group but still positive in the majority of adjacent lung tissue specimens (25 of 30) and achieved up to 39 % of cells. Conclusion. We suggest that TUBB3 expression in adjacent morphologically normal lung tissue indicates presence of transformed and potentially malignant cells far from the primary site.

About the Authors

I. A. Mamichev
N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia
Russian Federation


T. A. Bogush
N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia
Russian Federation


E. A. Dudko
N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia
Russian Federation


O. M. Ryabinina
N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia
Russian Federation


A. N. Grishanina
N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia
Russian Federation


V. E. Kirsanov
N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia
Russian Federation


B. E. Polotsky
N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia
Russian Federation


M. M. Davydov
N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia
Russian Federation


References

1. Nogales E. Structural insights into microtubule function. Annu Rev Biochem 2000;69:277-302. PMID:10966460.

2. Leandro-Garcia L.J., Leskela S., Landa I. et al. Tumoral and tissue-specific expression of the major human beta-tubulin isotypes. Cy-toskeleton (Hoboken) 2010;67(4):214-23. doi: 10.1002/cm.20436. PMID: 20191564.

3. Jakobsen J.N., Santoni-Rugiu E., Sorensen J.B. Use of TUBBIII for patient stratification and prognosis in lung cancer. Lung Cancer Management 2015;4(2): 97-110. doi:10.2217/lmt.15.6.

4. Derry W.B., Wilson L., Khan I.A. et al. Taxol differentially modulates the dynamics of microtubules assembled from unfractionated and purified beta-tubulin isotypes. Biochemistry 1997;36(12):3554-62. PMID: 9132006.

5. Carre M., Andre N., Carles G. et al. Tubulin is an inherent component of mitochondrial membranes that interacts with the voltage-dependent anion channel. J Biol Chem 2002; 13;277(37):33664-9. Epub 2002 Jun 26. PMID: 12087096.

6. Luduena R.F. A Hypothesis on the Origin and Evolution of Tubulin. Int Rev Cell Mol Biol 2013;302:41-185. doi: 10.1016/B978-0-12-407699-0.00002-9. PMID: 23351710.

7. McCarroll J.A., Gan P.P., Erlich R.B. et al. TUBB3/pIII-tubulin acts through the PTEN/ AKT signaling axis to promote tumorigenesis and anoikis resistance in non-small cell lung cancer. Cancer Res 2015;75(2):415-25. doi: 10.1158/0008-5472.CAN-14-2740. Epub 2014 Nov 20. PMID: 25414139.

8. Богуш Т.А., Шатурова А.С., Дудко Е.А. и др. Количественная иммунофлуо-ресцентная оценка с использованием проточной цитофлуориметрии экспрессии эстрогеновых рецепторов р в солидных опухолях человека. Вестник московского университета, cер. 2. Химия 2011;52(4): 305-12.


Review

For citations:


Mamichev I.A., Bogush T.A., Dudko E.A., Ryabinina O.M., Grishanina A.N., Kirsanov V.E., Polotsky B.E., Davydov M.M. Immunofluorescent analyses of tumor marker beta-III tubuilin expression in tumor and ajacent normal lung tissue derived from patients with non-small cell lung cancer. Russian Journal of Biotherapy. 2016;15(2):16-18. (In Russ.) https://doi.org/ 10.17650/1726-9784-2016-15-2-16-18

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ISSN 1726-9784 (Print)
ISSN 1726-9792 (Online)