HER2/p53 ratios among canine mammary tumours and respective derived cell culture

Silmara Sanae Sakamoto; Letícia Colin Panegossi; Roberto Gameiro de Carvalho; Tereza Cristina Cardoso

doi:10.29327/multiscience.2022001

Keywords:

cancer markers

cell phenotype

culture

Abstract

In this study, the expression of p53 and human epidermal growth factor receptor 2 (HER2) proteins were investigated in different canine mammary tumors (CMT) and cell cultures derived from them, for the purpose of determining neoplastic behavior in vitro. For this purpose, immunohistochemistry and immunocytochemistry were performed and results were compared according to histological diagnose. CMT were collected and divided into two halves, one for histological and immunohistochemistry analyses and another for cell cultures. Cell markers p53 and HER2 proteins were detected by immunohistochemistry in the original tumors and immunocytochemistry in CMT-derived cell lines. A total of CMT (n = 17) were classified and divided into benign mixed tumor (BMT), complex carcinoma (CC), simple carcinoma (SC), and squamous cell carcinoma (SCC). Low expression of p53 was verified in BMT and CC, averagely in SC and undetectable in SCC. In vitro, there was an increase in p53 expression by cultured cells. However, HER2 protein expression was not significant in BMT, CC and SCC. In contrast, MCT-derived cells were considered HER2-positive in all MCT types. In conclusion, the in vitro model is essential for the study of neoplastic behavior and understanding of the carcinogenic mechanisms that occur in vivo.
References
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7. Hayden A, Johnson PWM, Packham G, Crabb SJ (2011) S-adenosylhomocysteine hydrolase inhibition by 3-deazaneplanocin A analogues induces anti-cancer effects in breast cancer cell lines and synergy with both histone deacetylase and HER inhibition. Breast Cancer Research and Treatment 127:109-119.
8. Hellmén E, Moller M, Blankenstein A, Andersson L, Bengt W (2000) Expression of different phenotypes in cell lines from canine mammary spindle-cell tumours and osteosarcomas indicating a pluripotent mammary stem cell origin. Breast Cancer Research and Treatment 61:197-210.
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10. Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW (1991) Participation of p53 protein in the cellular response in DNA damage. Cancer Research 51:6304-6311.
11. Kim JH, Im KS, Yhee JY, Nho WG, Sur JH (2011) Expression of HER-2 and nuclear localization of HER-3 protein in canine mammary tumours: Histopathological and immunohistochemical study. Veterinary Journal 180:318-322.
12. Król M, Pawloski KM, Majchrzak K, Gajewska M, Majewska A, Moty T (2012) Global gene expression profiles of canine macrophages and canine mammary cancer cells grown as a co-culture in vitro. BMC Veterinary Research 8:16.
13. Krol M, Pawlowski KM, Skierski J, Rao NAS, Hellmén E, Mol JA, Motyl T (2009) Transcriptomic profile of two canine mammary cancer cell lines with different proliferation and anti-apoptotic potential. Journal of Physiology and Pharmacology 60:95-106.
14. Kumaraguruparan R, Prathiba D, Nagini S (2006) Of humans and canines: immunohistochemical analysis of PCNA, Bcl-2, p53, cytokeratin and ER in mammary tumours. Research in Veterinary Science 81:218-224.
15. Lacroix M, Leclerq G (2004) Relevance of breast cancer cell lines as models for breast tumours: an update. Breast Cancer Research and Treatment 83:249-289.
16. Lee CH, Kim WH, Lim JH, Kang MS, Kim DY, Kweon OK (2004) Mutation and overexpression of p53 as a prognostic factor in canine mammary tumors. Journal of Veterinary Science 5:63-69.
17. Linjawi A, Kontogiannea M, Halwani F, Edwardes M, Meterissian S (2004) Prognostic significance of P53, Bcl-2 and Bax expression in early breast cancer. Journal of the American College of Surgeons 198:83-90.
18. Midsorp W, Else RW, Hellmén E, Lipscomb TP (1999) Histological classification of mammary tumors of the dog and cat. 2nd ed. Armed Forces Institute of Pathology Washington DC in cooperation with the American Registry of Pathology and the World Health Organization Reference on Comparative Oncology 7:58.
19. Pawlowski KM, Krol M, Majewska A, Badowska-Kozakiewicz A, Mol JA, Malicka E, Motyl T (2009) Comparison of cellular and tissue transcriptional profiles in canine mammary tumor. Journal of Physiology and Pharmacology 60:85-94.
20. Ressel L, Puleio R, Ruggero G, Vannozzi I, Millanta F, Caracappa S, Poli A (2013) HER-2 expression in canine morphologically normal, hyperplastic and neoplastic mammary tissues and its correlation with the clinical outcome. Research in Veterinary Science 94:299-305.
21. Shafiee R, Javanbakht J, Atyabi N, Kheradmard P, Khiradmand D, Bahrami A, Daraei H, Khadivar F (2013) Diagnosis, classification and grading of canine mammary tumours as a model to study human breast cancer: a clinico-cytohistopathological study with environmental factors influencing public health and medicine. Cancer Cell International 13:79.
22. Sleeckx N, de Rooster H, Veldhuis Kroeze EJB, Van Ginneken C, Van Brantegem L (2011) Canine mammary tumours, an overview. Reproduction in Domestic Animals 46:1112-1131.
23. Thompson EW, Sung V, Lavigne M, Baumann K, Azumi N, Aaron AD, Clarke R (1999) LCC15-MB a vimentin-positive human breast cancer line from a femoral bone metastasis. Clinical & Experimental Metastasis 17:193-204.
24. Wensman H, Flama V, Pejler G, Hellmén E (2008) Plasticity of cloned canine mammary spindle cell tumor, osteosarcoma and carcinoma cells. Veterinary Pathology 45:803-815.

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

How to cite

Sakamoto, S. S., Panegossi, L. C., de Carvalho, R. G., & Cardoso, T. C. (2021). HER2/p53 ratios among canine mammary tumours and respective derived cell culture. Multidisciplinary Science Journal, 4(1), 2022001. https://doi.org/10.29327/multiscience.2022001

[1] Ackland ML, Newgreen DF, Fridman M, Waltham MC, Arvanitis A, Minichiello J, Price JT, Thompson EW (2003) Epidermal growth factor induced epithelia-mesenchymal transition in human breast carcinoma cells. Laboratory Investigation 83:435-448.

[2] Andrade FHE, Figueroa FC, Bersano PRO, Bissacot DZ, Rocha NS (2010) Malignant mammary tumor in female dogs: environmental contaminants. Diagnostic Pathology 5:45.

[3] Bertagnolli AC, Cassali GD, Genelhu CLS, Costa FA, Oliveira JFC, Gonçalves PBD (2009) Immunohistochemical expression of p63 and ΔNp63 in mixed tumours of canine mammary glands and its relation with p53 expression. Veterinary Pathology 46:407-415.

[4] Citri A, Yarden Y (2006) EGF-ERBB signaling: towards the systems level. Nature Reviews Molecular Cell Biology 7:505-516.

[5] Dagli MLZ (2008) The search for suitable prognostic markers for canine mammary tumors: a promising outlook. Veterinary Journal 177:3-5.

[6] Goldschmidt M, Peña L, Rasotto R, Zappulli V (2011) Classification and grading of canine mammary tumors. Veterinary Pathology 48:117-131.

[7] Hayden A, Johnson PWM, Packham G, Crabb SJ (2011) S-adenosylhomocysteine hydrolase inhibition by 3-deazaneplanocin A analogues induces anti-cancer effects in breast cancer cell lines and synergy with both histone deacetylase and HER inhibition. Breast Cancer Research and Treatment 127:109-119.

[8] Hellmén E, Moller M, Blankenstein A, Andersson L, Bengt W (2000) Expression of different phenotypes in cell lines from canine mammary spindle-cell tumours and osteosarcomas indicating a pluripotent mammary stem cell origin. Breast Cancer Research and Treatment 61:197-210.

[9] Hsu W-L, Huang H-M, Liao J-W, Wong M-L, Chang S-C (2009) Increased survival in dogs with malignant HER-2 protein and detection of a silent single nucleotide polymorphism in the canine HER-2 gene. Veterinary Journal 180:116-123.

[10] Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW (1991) Participation of p53 protein in the cellular response in DNA damage. Cancer Research 51:6304-6311.

[11] Kim JH, Im KS, Yhee JY, Nho WG, Sur JH (2011) Expression of HER-2 and nuclear localization of HER-3 protein in canine mammary tumours: Histopathological and immunohistochemical study. Veterinary Journal 180:318-322.

[12] Król M, Pawloski KM, Majchrzak K, Gajewska M, Majewska A, Moty T (2012) Global gene expression profiles of canine macrophages and canine mammary cancer cells grown as a co-culture in vitro. BMC Veterinary Research 8:16.

[13] Krol M, Pawlowski KM, Skierski J, Rao NAS, Hellmén E, Mol JA, Motyl T (2009) Transcriptomic profile of two canine mammary cancer cell lines with different proliferation and anti-apoptotic potential. Journal of Physiology and Pharmacology 60:95-106.

[14] Kumaraguruparan R, Prathiba D, Nagini S (2006) Of humans and canines: immunohistochemical analysis of PCNA, Bcl-2, p53, cytokeratin and ER in mammary tumours. Research in Veterinary Science 81:218-224.

[15] Lacroix M, Leclerq G (2004) Relevance of breast cancer cell lines as models for breast tumours: an update. Breast Cancer Research and Treatment 83:249-289.

[16] Lee CH, Kim WH, Lim JH, Kang MS, Kim DY, Kweon OK (2004) Mutation and overexpression of p53 as a prognostic factor in canine mammary tumors. Journal of Veterinary Science 5:63-69.

[17] Linjawi A, Kontogiannea M, Halwani F, Edwardes M, Meterissian S (2004) Prognostic significance of P53, Bcl-2 and Bax expression in early breast cancer. Journal of the American College of Surgeons 198:83-90.

[18] Midsorp W, Else RW, Hellmén E, Lipscomb TP (1999) Histological classification of mammary tumors of the dog and cat. 2nd ed. Armed Forces Institute of Pathology Washington DC in cooperation with the American Registry of Pathology and the World Health Organization Reference on Comparative Oncology 7:58.

[19] Pawlowski KM, Krol M, Majewska A, Badowska-Kozakiewicz A, Mol JA, Malicka E, Motyl T (2009) Comparison of cellular and tissue transcriptional profiles in canine mammary tumor. Journal of Physiology and Pharmacology 60:85-94.

[20] Ressel L, Puleio R, Ruggero G, Vannozzi I, Millanta F, Caracappa S, Poli A (2013) HER-2 expression in canine morphologically normal, hyperplastic and neoplastic mammary tissues and its correlation with the clinical outcome. Research in Veterinary Science 94:299-305.

[21] Shafiee R, Javanbakht J, Atyabi N, Kheradmard P, Khiradmand D, Bahrami A, Daraei H, Khadivar F (2013) Diagnosis, classification and grading of canine mammary tumours as a model to study human breast cancer: a clinico-cytohistopathological study with environmental factors influencing public health and medicine. Cancer Cell International 13:79.

[22] Sleeckx N, de Rooster H, Veldhuis Kroeze EJB, Van Ginneken C, Van Brantegem L (2011) Canine mammary tumours, an overview. Reproduction in Domestic Animals 46:1112-1131.

[23] Thompson EW, Sung V, Lavigne M, Baumann K, Azumi N, Aaron AD, Clarke R (1999) LCC15-MB a vimentin-positive human breast cancer line from a femoral bone metastasis. Clinical & Experimental Metastasis 17:193-204.

[24] Wensman H, Flama V, Pejler G, Hellmén E (2008) Plasticity of cloned canine mammary spindle cell tumor, osteosarcoma and carcinoma cells. Veterinary Pathology 45:803-815.

Abstract

References

How to cite