Morphofunctional activity of npm1 protein in tubularbreast cancer in cats
https://doi.org/10.52419/issn2072-2419.2024.3.216
Abstract
The carcinogenesis of mammary gland tumors in cats is characterized by its uniformity with respect to cellular structures, due to this, it is possible to analyze the effect of individual signature patterns on the mechanism of cancer occurrence well. To do this, it is necessary to determine the functional state of individual proteins that begin to express both inside and on the surface of the nuclear structure. Some multifunctional proteins in the region of nucleolar organizers form the activity of the nucleus, which is closely related to the regulation of the cell cycle. The nucleophosmin protein is an essential cellular protein that is involved in a number of pathways, including mRNA transport, chromatin remodeling, apoptosis, and genome stability. It is poorly expressed by resting cells, but its overexpression leads the cell to stimulate division and increase metastatic potential. Therefore, the aim of our study was to study the expression of the nucleophosmin protein (NPM1) at different histological gradations of tubular carcinoma in mammary glands in cats (n=13). The review presents the results of the histological structure of tubular carcinoma from the highly differentiated to the low-differentiated type. When studying the material, it was revealed that tumor emboli were recorded in 5 samples of G3 tumors in lymphatic vessels that were located cross-border, and macrometastasis, occupying about 70% of the parenchyma of the cortical substance, was also recorded in one sample of the lymph node. When performing an immunohistochemical study (IHC), it was determined that immunopositive sites were noted in the nucleolar localization, while a staining score was recorded, which corresponded to moderate (++) for highly differentiated tumors and strong (+++) for low-grade ones. Thus, when this marker was overexpressed, chromatin disorganization occurred in the nucleolus with an increase in subcomputments in the nucleus, which subsequently led to an increase in the metastatic potential characteristic of G3 tumors.
About the Authors
V. V. MitenkoRussian Federation
Mitenko V.V. – Candidate of Biological Sciences, ass. of the Department of Parasitology and Veterinary Medicine, Anatomy and Pathanatomy named after Professor S.N. Nikolsky
O. V. Dilekova
Russian Federation
Dilekova O.V. – Doctor of Biological Sciences, Head of the Department of Parasitology and Veterinary Medicine, Anatomy and Pathanatomy named after Professor S.N. Nikolsky
References
1. Cancer driver genes IDH1/2, JARID1C/ KDM5C and UTX/KDM6A: crosstalk between histone demethylation and hypoxic reprogramming in cancer metabolism / Chang S., Yim S., Park H. // Exp Mol Med. 2019. – Т. 51. – №6. – С. 1-17.
2. Extensive analysis of tumor array confirms overwhelming role of nucleophosmin in breast cancer / Karhemo Piia-Riitta, Rivinoja Antti, Lundin Johan, Joensuu Heikki Bono, Petri, Laakkonen // Regular article oncogenesis and tumor progression. – 2011.– Т. 179. – № 2. – С. 1004-1014.
3. Histone deacetylase inhibitor eliminates multidrug resistance by reducing nucleophosmin levels via the PI3K/Akt pathway in breast cancer / Chen Xi, Zheng Hu, Cai J.H., Zhang WP, Yu HS, Xing J.F., Dong Y.L. // Int J Oncol. 2016. – Т. 49. – №1. – С. 294-304.
4. Invasive micropapillary breast carcinoma in cats: clinical and pathological features and nuclear DNA content / Seixas F., Palmeira S., Pires M.A., Lopez S. // Veterinary pathology. – 2007. – T. 44. – №6. – S. 842-848.
5. Limaiem F, Mlika M. Tubular Breast Carcinoma. 2023 Jan 1. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 31194380.
6. Nucleophosmin, a multifunctional nucleolar organizer with a role in DNA repair / David J. López, José A. Rodríguez, Sonia Bañuelos // Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 2020. – Т.1868. – №12. – с. 21-32.
7. Nucleophosmin: from structure and function to disease development / Box JK, Paquet N, Adams MN, Boucher D, Bolderson E, O'Byrne KJ, Richard DJ. // BMC Mol Biol. 2016. – Т.17.– № 1. – С. 19-34.
8. Proposed Classification of the Feline “Complex” Mammary Tumors as Ductal and Intraductal Papillary Mammary Tumors / Zappulli V, Caliari D, Rasotto R, Ferro S, Castagnaro M, Goldschmidt M. // Veterinary Pathology. – 2013. –Т. 50. – №6. – S.1070-1077.
9. The contribution of overexpression of nucleophosmin to multidrug resistance in breast cancer / Chen S., Meng T., Zheng X, Cai J., Zhang V, Yu Ch, Xing J., Dong Yu. // J is a drug target. 2018. – Т. 26. – № 1. – С. 27-35.
10. Argyrophilic proteins of the regions of nucleolar organizers – markers of the rate of cell proliferation: A review / Aikhlin N.T., Bukaeva I.A., Probatova N.A. // Arch. Pathol. – 2006. – Vol.68. – No. 3. – pp. 47-51. (In Russ.)
11. Nucleophosmin and nucleolin: coding genes and expression in various tissues of animals and humans / Zenit-Zhuravleva E.G., Polkovnichenko E.M., Lushnikova A.A., Treshchalina E.M., Bukaeva I.A., Raikhlin N.T.. // Molecular medicine – 2012. – No. 4. – pp. 19-25. (In Russ.)
12. Mammary gland tumors of cats and dogs: morphological features / E.P. Shapiro, N.A. Krasnoslobodtsev, N.S. Kukharenko [et al.] // Topical issues and innovative technologies in veterinary medicine, animal husbandry and nature conservation complex: mater. international scientific and practical conference, dedicated. the 40th anniversary of the establishment of the veterinary Faculty. Ussuriysk, -2019. – pp. 138-144. (In Russ.)
Review
For citations:
Mitenko V.V., Dilekova O.V. Morphofunctional activity of npm1 protein in tubularbreast cancer in cats. International Journal of Veterinary Medicine. 2024;(3):216-222. (In Russ.) https://doi.org/10.52419/issn2072-2419.2024.3.216