Skip to main content

Advertisement

Log in

Immunohistochemical Study of Phospho-Stat3-ser727 Expression in Feline Mammary Gland Tumours

  • Published:
Veterinary Research Communications Aims and scope Submit manuscript

Abstract

We describe the expression of pStat3-ser727 (signal transducer and activator of transcription 3 phosphorylated on serine 727) in normal, hyperplastic and neoplastic feline mammary gland tissue assessed by immunohistochemistry in 56 cats. The samples included 4 normal mammary non-lactating tissues, 13 hyperplastic lesions (9 lobular and 4 fibroepithelial) and 39 tumours (6 benign and 33 carcinomas). For immunohistochemistry, tissue sections were incubated with anti-pStat3-ser727 monoclonal antibodies and visualized with EnVision-DAB polymer. pStat3-ser727 positivity was quantified in a semi-quantitative manner, differentiating cytoplasmic and nuclear localization. Intense anti-pStat3-ser727 immunoreactivity was detected in epithelial neoplastic cells and in the fibro-component in two fibroepithelial hyperplastic lesions. The immunostaining was dot-like in the cytoplasm and homogeneous in the nuclei in both benign and malignant lesions. Statistically significant relations were observed between nuclear expression of pStat3-ser727 and the pleomorphism score (p = 0.006), mitotic activity (p < 0.0001), and histological grade (p < 0.0001). In contrast, no significant correlations were observed for cytoplasmic pStat3-ser727. These findings add new and interesting information on the potential role of the phosphorylated form of Stat3 in malignant lesions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

BSA:

bovine serum albumin

CSF-1:

colony-stimulating factor-1

DAB:

3,3′-diaminobenzide tetrahydrochloride

EGFr:

epidermal growth factor receptor

IFN:

interferon

FMLP:

N-formyl-methionyl-leucyl-phenylalanine

MAPK:

mitogen-activated protein kinase

PBS:

phosphate-buffered saline

PDGFR:

platelet-derived growth factor receptor

pStat3-ser727:

phosphorylated signal transducer and activator of transcription 3-serine 727

Stat3:

signal transducers and activators of transcription 3

TBS:

Tris-buffered saline

TNF:

tumour necrosis factor

WHO:

World Health Organization

References

  • Berclaz, G., Altermatt, H.J., Rohrbach, V., Siragusa, A., Dreher, E. and Smith, P.D., 2001. EGFR dependent expression of Stat3 (but not Stat1) in breast cancer. International Journal of Oncology, 19, 1155–1160

    PubMed  CAS  Google Scholar 

  • Boulton, T.G., Zhong, Z., Wen, Z., Darnell, J.E. Jr., Stahl, N. and Yancopoulos, G.D., 1995. STAT3 activation by cytokines utilizing gp130 and related transducers involves a secondary modification requiring an H7-sensitive kinase. Proceedings of the National Academy of Science of the USA, 92, 6915–6919

    Article  CAS  Google Scholar 

  • Chung, J., Uchida, E., Grammer, T.C. and Blenis, J., 1997. STAT3 serine phosphorylation by ERK-dependent and -independent pathways negatively modulates its tyrosine phosphorylation. Molecular and Cellular Biology, 17, 6508–6516

    PubMed  CAS  Google Scholar 

  • Dias Pereira, P., Carvalheira, J. and Gärtner, F., 2004. Cell proliferation in feline normal, hyperplastic and neoplastic mammary tissue—an immunohistochemical study. The Veterinary Journal, 168, 180–185

    Article  PubMed  CAS  Google Scholar 

  • Elston, C.W. and Ellis, I.O., 1996. Assessment of histological grade. In: P.P. Rosen (ed.), Rosen's Breast Pathology, (Lippincott Raven, Philadelphia), 365–382

    Google Scholar 

  • Frank, D.A., Mahajan, S. and Ritz, J., 1997. B lymphocytes from patients with chronic lymphocytic leukaemia contain signal transducer and activator of transcription (STAT) 1 and STAT3 constitutively phosphorylated on serine residues. Journal of Clinical Investigation, 100, 3140–3148

    Article  PubMed  CAS  Google Scholar 

  • Gao, H., Guo, R.-F., Speyer, C.L., Reuben, J., Neff, T.A., Hoesl, L.M., Riedermann, N.C., McClintock, S.D., Sarma, J.V., Van Rooijen, N.V., Zetoune, F.S. and Ward, P.A., 2004. Stat3 activation in acute lung injury. The Journal of Immunology, 172, 7703–7712

    PubMed  CAS  Google Scholar 

  • Garcia, R. and Jove, R., 1998. Activation of STAT transcription factors in oncogenic tyrosine kinase signalling. Journal of Biomedical Science, 5, 79–85

    Article  PubMed  CAS  Google Scholar 

  • Hirano, T., Ishihara, K. and Hibi, M., 2000. Roles of Stat3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors. Oncogene, 19, 2548–2556

    Article  PubMed  CAS  Google Scholar 

  • Jain, N., Zhang, T., Fong, S.L., Lim, C.P. and Cao, X., 1998. Repression of Stat3 activity by activation of mitogen-activated protein kinase (MAPK). Oncogene, 17, 3157–3167

    Article  PubMed  CAS  Google Scholar 

  • Kimmelman, A., Bafico, A. and Aaronson, S.A., 2001. Oncogenes and Signal Transduction. In: J. Mendelsohn, P.M. Howley, M.A. Israel, and L.A. Liotta (eds), The Molecular Basis of Cancer, (W.B. Saunders, Philadelphia)

    Google Scholar 

  • Kuroki, M. and O'Flaherty, J.T., 1999. Extracellular signal-regulated protein kinase (ERK)-dependent and ERK-independent pathways target STAT3 on serine-727 in human neutrophils stimulated by chemotactic factors and cytokines. Biochemical Journal, 341, 691–696

    Article  PubMed  CAS  Google Scholar 

  • Levy, D.E. and Lee, C.K., 2002. What does Stat3 do? Journal of Clinical Investigation, 109, 1143–1148

    Article  PubMed  CAS  Google Scholar 

  • Misdorp, W., Else, R.W., Hellemen, E. and Lipscomb, T.P., 1999. Histological Classification of Mammary Tumors of the Dog and the Cat. 2nd edn, (Armed Forces Institute of Pathology, Washington, DC).

    Google Scholar 

  • Petterino, C., Martini, M. and Castagnaro, M., 2001. Stat3 expression in canine mammary gland tumors and mammary gland hyperplasia. European Journal of Veterinary Pathology, 7, 117–122

    Google Scholar 

  • Petterino, C., Rossetti, E. and Drigo, M., 2006. Immunodetection of the signal transducer and activator of transcription-3 in canine haemangioma and haemangiosarcoma. Research in Veterinary Science, 80, 186–188

    Article  PubMed  CAS  Google Scholar 

  • Petterino, C., Ratto, A., Arcicasa, E., Podestà, G., Drigo, M. and Pellegrino, C., 2005a. Expression of Stat3 in feline mammary gland tumours and its relation to histologic grade. Veterinary Research Communications (in press)

  • Petterino, C., Martano, M., Cascio, P., Cerruti, F., Martini, M., Morello, E., Bruno, R., Castagnaro, M. and Buracco, P., 2005b. Immunnohistochemical study of STAT3 expression in feline injection-site fibrosarcomas. Journal of Comparative Pathology (in press)

  • Porras, A., Zuluaga, S., Black, E., Valladares, A., Alvarez, A.M., Ambrosino, C., Benito, M. and Nebreda, A.R., 2004. P38 alpha mitogen-activated protein kinase sensitizes cells to apoptosis induced by different stimuli. Molecular and Cellular Biology, 15, 922–933

    CAS  Google Scholar 

  • Sartor, C.I., Dziubinski, M.L., Yu, C.L., Jove, R. and Ethier, S.P., 1997. Role of epidermal growth factor receptor and Stat-3 activation in autonomous proliferation of SUM-102PT human breast cancer cells. Cancer Research, 57, 978–987

    PubMed  CAS  Google Scholar 

  • Su, L., Rickert, R.C. and David, M., 1999. Rapid STAT phosphorylation via the B cell receptor. The Journal of Biological Chemistry, 274, 31770–31774

    Article  PubMed  CAS  Google Scholar 

  • Turkson, J., Bowman, T., Adnane, J., Zhang, Y., Djeu, J.Y., Sekharam, M., Frank, D.A., Holzman, L.B., Wu, J., Sebti, S. and Jove, R., 1999. Requirement for Ras/Rac1-mediated p38 and c-Jun N-terminal kinase signalling in Stat3 transcriptional activity induced by the Src oncoprotein. Molecular and Cellular Biology, 19, 7519–7528

    PubMed  CAS  Google Scholar 

  • Watson, C.J. and Miller, W.R., 1995. Elevated levels of members of the STAT family of transcription factors in breast carcinoma nuclear extracts. British Journal of Cancer, 71, 840–844

    PubMed  CAS  Google Scholar 

  • Wen, Z., Zhong, Z. and Darnell, J.E. Jr., 1995. Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell, 82, 241–250.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to C. Petterino.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Petterino, C., Podestà, G., Ratto, A. et al. Immunohistochemical Study of Phospho-Stat3-ser727 Expression in Feline Mammary Gland Tumours. Vet Res Commun 31, 173–184 (2007). https://doi.org/10.1007/s11259-006-3330-4

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11259-006-3330-4

Keywords

Navigation