The effects of various kinase and phosphatase inhibitors on the transmission of the prolactin and extracellular matrix signals to rabbit αS1-casein and transferrin genes

Bayat-Sarmadi, Mahasti; Puissant, C.; Houdebiné, Louis‐Marie

doi:10.1016/1357-2725(95)00034-m

Cited by 10 publications

(8 citation statements)

References 41 publications

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“…As our manuscript was being revised, another group reported that, although STAT3 DNA binding is not blocked by H7, transcriptional activation is blocked. In contrast, our results with PKC inhibitors H7 and GF 109203X indicate that PKC does not play a role in ␤-casein expression (1,71,72). These observations are consistent with very low PKC activity in mammary cells during late pregnancy and lactation, periods closely associated with the expression of milk protein genes (58).…”

Section: Discussioncontrasting

confidence: 55%

“…Moreover, our data indicate that the binding activity of MGF does not strictly reflect its ability to induce casein gene expression. These data and our other results (71) suggest that a tyrosine phosphatase is also involved in triggering the induction of casein gene expression.…”

Section: Figsupporting

confidence: 59%

“…However, our results, demonstrating the activation of MGF in secondary cultures where ECM proteins are not detectable 4 (under conditions where only limited casein synthesis occurs), suggest that ECM exerts its effect on casein genes expression independently of MGF activation. Furthermore, our results suggest that ECM signaling is distinct from that of PRL (71).…”

Section: Discussionmentioning

confidence: 62%

“…Interestingly, some enhancement of existing basal level of casein gene transcription, generally observed in mammary explants, is detected after 24 h of PV treatment (71). These data strongly implicate other factors involved in PV activity, such as positive or negative regulators.…”

Section: Figmentioning

confidence: 54%

“…Thus it is not still clear if the MGF activity depend essentially on tyrosine phosphorylation event or serine/threonine phosphorylations could also be required. Therefore, we used several protein-tyrosine or serine/ threonine kinase inhibitors, which have been shown recently to abrogate or not to abrogate the induction of rabbit ␣S1-and ␤-casein genes in cultures of mammary epithelial cells (1,71). MGF activity was evaluated in cells cultured in synthetic medium and induced by PRL for 20 h, followed by treatment with inhibitors (Fig.…”

Section: Mgf Activation By Prl Is Affected By the Protein-tyrosine Kimentioning

confidence: 99%

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Activation of STAT Factors by Prolactin, Interferon-γ, Growth Hormones, and a Tyrosine Phosphatase Inhibitor in Rabbit Primary Mammary Epithelial Cells

Schindler

Larose

et al. 1995

Journal of Biological Chemistry

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In numerous studies on mammary epithelial cell lines multiple factors, added to the medium or contained in the serum, were required for casein gene expression. It has been shown in these systems that the mammary gland factor (MGF) is implicated in the activation of the ␤-casein gene promoter. In the present study, we determined the relationship between known agents that affect casein gene expression and MGF activity using the properties of rabbit primary mammary epithelial cells to respond to PRL alone, when cultured in chemically defined medium. We demonstrate that MGF is rapidly activated by PRL alone or by human growth hormone, a natural ligand of many PRL receptors (PRL-Rs), in the cytoplasm and accumulated in the nucleus. The MGF activation by PRL occurred in the absence of endogenous extracellular matrix, a condition where casein synthesis is known to be markedly reduced. Different inhibitors of protein-tyrosine kinases, which have been shown to reduce casein mRNA synthesis, but not of protein kinase C, decrease the MGF activity. A tyrosine phosphatase inhibitor, sodium pervanadate, induced two GAS-binding complexes related to MGF and STAT1. Our data show that MGF is a latent cytoplasmic factor rapidly activated in mammary epithelial cells, by a mechanism involving a tyrosine kinase and a tyrosine phosphatase.

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Section: Discussioncontrasting

confidence: 55%

Section: Figsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 62%

Section: Figmentioning

confidence: 54%

Section: Mgf Activation By Prl Is Affected By the Protein-tyrosine Kimentioning

confidence: 99%

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Activation of STAT Factors by Prolactin, Interferon-γ, Growth Hormones, and a Tyrosine Phosphatase Inhibitor in Rabbit Primary Mammary Epithelial Cells

Schindler

Larose

et al. 1995

Journal of Biological Chemistry

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Extracellular matrix regulates alpha s1‐casein gene expression in rabbit primary mammary cells and CCAAT enhancer binding protein (C/EBP) binding activity

Jolivet¹,

Meusnier²,

Chaumaz³

et al. 2001

J of Cellular Biochemistry

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Previous studies have shown that both the signal transducer and activator of transcription 5 (STAT5) and the CCAAT enhancer binding proteins (C/EBPs) are involved in the regulation of casein gene expression by mammary epithelial cells. Prolactin (Prl) activation of STAT5 is necessary for casein gene expression. The extracellular matrix (ECM) regulates also casein gene expression. Here, we have investigated whether ECM regulates C/EBPs activity in primary rabbit mammary epithelial cells. Isolated primary mammary cells were cultured on plastic or on floating collagen I gel. Prolactin induced alphas 1-casein gene expression when cells were cultured on collagen but not on plastic. It is noteworthy that activated STAT5 was detected in both culture conditions. Several STAT5 isoforms (STAT5a, STAT5b, and other STAT5 related isoforms, some with lower molecular weight than the full-length STAT5a and STAT5b) were detected under the different culture conditions. However, their presence was not related to the expression of alphas 1-casein gene. The binding of nuclear factors to a C/EBP specific binding site and the protein level of C/EBPbeta differed in cells cultured on plastic or on collagen but these parameters were not modified by Prl. This suggests that C/EBP binding activity was regulated by ECM and not by Prl. Interestingly, these modifications were correlated to the expression of the alphas 1-casein gene. Hence, the activation of the alphas 1-casein gene expression depends on two independent signals, one delivered by Prl via the activation of STAT5, the other delivered by ECM via C/EBP.

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Regulation by the extracellular matrix (ECM) of prolactin‐induced αs1‐casein gene expression in rabbit primary mammary cells: Role of STAT5, C/EBP, and chromatin structure

Jolivet¹,

Pantano

Houdebine³

2005

J of Cellular Biochemistry

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The aim of the present study was to understand how the extracellular matrix (ECM) regulates at the gene level the prolactin (Prl)-induced signal transducer and activator of transcription 5 (STAT5)-dependent expression of the alpha s1-casein gene in mammary epithelial cells. CCAAT enhancer binding proteins (C/EBPs) are assumed regulators of beta-casein gene expression. Rabbit primary mammary cells express alpha s1-casein gene when cultured on collagen and not on plastic. Similar C/EBPbeta, C/EBPdelta, STAT5, and Prl-activated STAT5 were found under all culture conditions. Thus the ECM does not act through C/EBPs or STAT5. This was confirmed by transfections of rabbit primary mammary cells by a construct sensitive to ovine prolactin (oPrl) and ECM (6i TK luc) encompassing STAT5 and C/EBP binding sites. The mutation of C/EBPs binding sites showed that these sites were not mandatory for Prl-induced expression of the construct. Interestingly, chromatin immunoprecipitation by the anti-acetylhistone H4 antibody (ChIP) showed that the ECM (and not Prl) maintained a high amount of histone H4 acetylation upstream of the alpha s1-casein gene especially at the level of a distal Prl- and ECM-sensitive enhancer. Alpha6 integrin (a membrane receptor of laminin, the principal active component of the mammary ECM) was found at the surface of cells cultured on collagen but not on plastic. In cells cultured on collagen in the presence of anti-alpha6 integrin antibody, Prl-induced transcription of the endogenous alpha s1-casein gene was significantly reduced, without modifying C/EBPs and STAT5. Besides, histone H4 acetylation was reduced. Thus, we propose that the ECM regulates rabbit alpha s1-casein protein expression by local modification of chromatin structure, independently of STAT5 and C/EBPs.

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The effects of various kinase and phosphatase inhibitors on the transmission of the prolactin and extracellular matrix signals to rabbit αS1-casein and transferrin genes

Cited by 10 publications

References 41 publications

Activation of STAT Factors by Prolactin, Interferon-γ, Growth Hormones, and a Tyrosine Phosphatase Inhibitor in Rabbit Primary Mammary Epithelial Cells

Activation of STAT Factors by Prolactin, Interferon-γ, Growth Hormones, and a Tyrosine Phosphatase Inhibitor in Rabbit Primary Mammary Epithelial Cells

Extracellular matrix regulates alpha s1‐casein gene expression in rabbit primary mammary cells and CCAAT enhancer binding protein (C/EBP) binding activity

Regulation by the extracellular matrix (ECM) of prolactin‐induced αs1‐casein gene expression in rabbit primary mammary cells: Role of STAT5, C/EBP, and chromatin structure

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