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

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 8505191 Publication Model: Print Cited Medium: Print ISSN: 0739-7240 (Print) Linking ISSN: 07397240 NLM ISO Abbreviation: Domest Anim Endocrinol Subsets: MEDLINE
    • Publication Information:
      Publication: Stoneham, Ma : Elsevier
      Original Publication: [Auburn, Ala.] : Domendo, Inc., c1984-
    • Subject Terms:
      Milk Proteins*; DNA-Binding Proteins/*metabolism ; Growth Hormone/*pharmacology ; Mammary Neoplasms, Animal/*metabolism ; Phosphotyrosine/*metabolism ; Trans-Activators/*metabolism; Amino Acid Sequence ; Animals ; Cell Differentiation/drug effects ; Cell Division/drug effects ; Dogs ; Gene Expression ; Humans ; Kinetics ; Molecular Sequence Data ; Phosphorylation ; Prolactin/pharmacology ; RNA/analysis ; Receptors, Prolactin/chemistry ; Receptors, Prolactin/genetics ; STAT5 Transcription Factor ; Sequence Homology ; Signal Transduction ; Tumor Cells, Cultured ; Tumor Suppressor Proteins
    • 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 tumor cells, which may indicate that GH induces differentiation in these tumor cells. The GH-induced activation of Stat5a and Stat5b in these cells, as part of the JAK/Stat signal transduction pathway, is consistent with mammary GH playing a role in autocrine and/or paracrine stimulation of (tumorous) mammary cells.
    • Accession Number:
      0 (DNA-Binding Proteins)
      0 (Milk Proteins)
      0 (Receptors, Prolactin)
      0 (STAT5 Transcription Factor)
      0 (STAT5A protein, human)
      0 (STAT5B protein, human)
      0 (Trans-Activators)
      0 (Tumor Suppressor Proteins)
      21820-51-9 (Phosphotyrosine)
      63231-63-0 (RNA)
      9002-62-4 (Prolactin)
      9002-72-6 (Growth Hormone)
    • Publication Date:
      Date Created: 20010420 Date Completed: 20010705 Latest Revision: 20191104
    • Publication Date:
      20250114
    • Accession Number:
      10.1016/s0739-7240(01)00088-1
    • Accession Number:
      11311850