Regulation and function of the cytokine-inducible SH-2 domain proteins, CIS and SOCS3, in mammary epithelial cells

Sibylle Tonko-Geymayer, Olivier Goupille, Martin Tonko, Claudia Soratroi, Akihiko Yoshimura, Charles Streuli, Andrew Ziemiecki, Reinhard Kofler, Wolfgang Doppler

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The cytokine-inducible src homology 2 (SH-2) proteins, CIS (cytokine inducible SH-2 domain protein) and SOCS3 (suppressor of cytokine signaling 3), are implicated in the negative regulation of prolactin (PRL) receptor-mediated activation of signal transducer and activator of transcription 5 (STAT5). We have studied the expression and function of CIS and SOCS3 proteins in the mouse mammary gland and in HC11 mammary epithelial cells. CIS and SOCS3 were differentially regulated: high expression levels of CIS mRNA were measured during the second half of pregnancy, whereas SOCS3 expression was high during the first 12 d post conceptum. SOCS3 levels increased, whereas CIS levels decreased, in the initial phase of involution. At the beginning of the lactation period both CIS and SOCS3 were high. PRL and epidermal growth factor (EGF) were able to induce CIS and SOCS3, whereas glucocorticoids inhibited their expression in mammary epithelial cells. The effect of EGF was much stronger on SOCS3 than on CIS. Ectopic expression of both SOCS3 and CIS inhibited STAT5 activation. Our data indicate that in the mammary gland CIS and SOCS3 are involved in regulating STAT5 signaling at three different instances: 1) SOCS3 serves as a mediator of the inhibitory EGF effect on PRL-induced STAT5 activation; 2) CIS and SOCS3 play a role as negative feedback inhibitors of PRL action; 3) Inhibition of CIS and SOCS3 expression by glucocorticoids contributes to the positive effect of glucocorticoids on PRL-induced STAT5 activation.

Original languageEnglish
Pages (from-to)1680-1695
Number of pages16
JournalMolecular Endocrinology
Volume16
Issue number7
DOIs
Publication statusPublished - 2002 Jan 1
Externally publishedYes

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src Homology Domains
Breast
Epithelial Cells
Cytokines
STAT5 Transcription Factor
Prolactin
Epidermal Growth Factor
Transcriptional Activation
Glucocorticoids
Human Mammary Glands
Suppressor of Cytokine Signaling 3 Protein
Prolactin Receptors
Lactation

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

Regulation and function of the cytokine-inducible SH-2 domain proteins, CIS and SOCS3, in mammary epithelial cells. / Tonko-Geymayer, Sibylle; Goupille, Olivier; Tonko, Martin; Soratroi, Claudia; Yoshimura, Akihiko; Streuli, Charles; Ziemiecki, Andrew; Kofler, Reinhard; Doppler, Wolfgang.

In: Molecular Endocrinology, Vol. 16, No. 7, 01.01.2002, p. 1680-1695.

Research output: Contribution to journalArticle

Tonko-Geymayer, S, Goupille, O, Tonko, M, Soratroi, C, Yoshimura, A, Streuli, C, Ziemiecki, A, Kofler, R & Doppler, W 2002, 'Regulation and function of the cytokine-inducible SH-2 domain proteins, CIS and SOCS3, in mammary epithelial cells', Molecular Endocrinology, vol. 16, no. 7, pp. 1680-1695. https://doi.org/10.1210/mend.16.7.0872
Tonko-Geymayer, Sibylle ; Goupille, Olivier ; Tonko, Martin ; Soratroi, Claudia ; Yoshimura, Akihiko ; Streuli, Charles ; Ziemiecki, Andrew ; Kofler, Reinhard ; Doppler, Wolfgang. / Regulation and function of the cytokine-inducible SH-2 domain proteins, CIS and SOCS3, in mammary epithelial cells. In: Molecular Endocrinology. 2002 ; Vol. 16, No. 7. pp. 1680-1695.
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AU - Tonko, Martin

AU - Soratroi, Claudia

AU - Yoshimura, Akihiko

AU - Streuli, Charles

AU - Ziemiecki, Andrew

AU - Kofler, Reinhard

AU - Doppler, Wolfgang

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