Growth hormone induces tyrosyl phosphorylation of the transcription factors Stat5a and Stat5b in CMT-U335 canine mammary tumor cells

Domestic Animal Endocrinology
E van GarderenJ A Schalken

Abstract

It has now been well documented that the normal and tumorous canine mammary glands can be extra-pituitary sites of substantial growth hormone (GH) synthesis. Until now, attempts to reproduce the GH synthesis in-vitro using canine mammary explants or mammary tumor cells have not been successful. Therefore, the response of CMT-U335 canine mammary tumor cells to administered porcine GH (pGH) was investigated as an in-vitro model to study the possible effects of GH synthesis on this site. CMT-U335 cells spontaneously express the growth hormone receptor (GHR) as well as the prolactin receptor (PRLR). Twenty five minutes after administration, GH induced, in a dose-dependent manner, phosphorylation of the transcription factors Stat5a and Stat5b. Clear phosphorylation was induced by 10(-7) M and 10(-8) M pGH, with virtually no phosphorylation at 10(-9) M pGH. A similar dose-dependent phosphorylation of Stat5a by ovine prolactin was found in these cells. Although at high concentrations binding of pGH to the canine PRLR can occur (albeit with a low pKa), the similar dose-dependent effect of oPRL on Stat5a phosphorylation indicated that pGH signaled through the GHR. Remarkably, pGH induced a moderately decreased proliferation of CMT-U335 ...Continue Reading

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Citations

Nov 15, 2002·Molecular and Cellular Endocrinology·Evert van Garderen, Jack A Schalken
Apr 13, 2010·Research in Veterinary Science·Felisbina L QueirogaJuan C Illera
Jun 29, 2012·Veterinary and Comparative Oncology·E MichelI M Reichler
Jun 26, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Young Kwang ChaeAmal Melhem-Bertrandt
Feb 7, 2019·Veterinary Ophthalmology·Juliana Kravetz de OliveiraFabiano Montiani-Ferreira
Dec 22, 2019·Cancers·Matthias KieslingerIwan A Burgener

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