Epidermal growth factor stimulates the prolactin synthesis and secretion in rat pituitary cells in culture (GH4C1 cells) by increasing the intracellular concentration of free calcium

Aanestad, M; Røtnes, Jan Sigurd; Torjesen, Peter A.; Haug, Egil; Sand, Olav; Bjøro, Trine

doi:10.1530/acta.0.1280361

Cited by 18 publications

(8 citation statements)

References 14 publications

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“…24 In the light of the putative mechanism underlying EGF actions in triggering this pathway, the question of a possible calpain (or other Ca 2+ -dependent proteases) involvement appears particularly important since it has been reported that an increase in the intracellular Ca 2+ concentrations mediates EGF effects on GH4C1 cells. 25 More generally, the results presented here taken together with the previously published data suggest a dual involvement of L-DNaseII in both apoptosis 15,17,19 and paraptosis (present study). It should be stressed that a dual involvement of CAD in both apoptosis and necrosis has also been reported in ischemic hippocampal neurons.…”

Section: Discussionsupporting

confidence: 87%

“…The latter hypothesis implies a hyperactivation of EGFR expressed on GH4C1 cells by a physiological concentration of EGF since we used this trophic factor in a nanomolar concentration (corresponding to the affinity of pituitary EGFR). 25,30 Future studies focused on the analysis of the functional consequences of such putative EGFR hyperactivation will certainly help understanding the molecular mechanisms linked with EGFassociated malignant transformation.…”

Section: Discussionmentioning

confidence: 99%

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A novel paraptosis pathway involving LEI/L-DNaseII for EGF-induced cell death in somato-lactotrope pituitary cells

et al. 2006

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We have recently reported that EGF triggers an original form of cell death in pituitary cell line (GH4C1) with a phenotype sharing some characteristics of both apoptosis (internucleosomal DNA fragmentation) and paraptosis (caspase-independence and cytoplasmic vacuolization). However, the endonuclease involved in EGF-induced DNA fragmentation has not been assessed so far. In the present work we therefore further explored the putative paraptosis involvement in EGF-induced cell death and asked whether L-DNaseII might be involved. Indeed, this endonuclease is known to mediate internucleosomal DNA fragmentation in caspase independent manner. Our Western blot, immunocytochemistry and enzymatic measurement assays show that EGF triggers a cleavage of Leukocyte Elastase Inhibitor (LEI) precursor into L-DNaseII, its subsequent enzymatic activation and nuclear translocation thus pointing to the involvement of this endonuclease pathway in caspase-independent DNA fragmentation. In addition, EGF-induced cell death can be blocked by paraptosis inhibitor AIP-1/Alix, but not with its anti-apoptotic C-terminal fragment (Alix-CT). Altogether these data suggest that EGF-induced cell death defines a novel, L-DNaseII-mediated form of paraptosis.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

A novel paraptosis pathway involving LEI/L-DNaseII for EGF-induced cell death in somato-lactotrope pituitary cells

et al. 2006

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“…The EGF-R has an intrinsic tyrosine kinase activity, and inhibition of tyrosine kinase activities has recently been shown to decrease [ 3 H]thymidine uptake in primary cultures of human pituitary adenomas ( Jones et al 1997). EGF can modulate the secretion of pituitary hormones in both normal (Ikeda et al 1984, Miyake et al 1985, Childs et al 1991 and tumor pituitary cells (Schonbrunn et al 1980, Aanestad et al 1993. Transforming growth factor-(TGF-), a member of the EGF family, which can thus also act through the EGF-R on target cells, has been detected in the normal pituitary gland (Kobrin et al 1987, Ezzat et al 1995, Fan & Childs 1995, and has been implicated in pituitary tumorigenesis (Finley & Ramsdell 1994).…”

Section: Introductionmentioning

confidence: 99%

Epidermal growth factor binding sites in human pituitary macroadenomas

Jaffrain-Rea

Petrangeli²,

Lubrano

et al. 1998

Journal of Endocrinology

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The number of epidermal growth factor (EGF) binding sites was determined by competitive binding assays in a series of 46 pituitary macroadenomas. A single concentration of 125 I-EGF (1 nM) was used for all experiments. In four cases, a displacement curve was obtained by adding increasing concentrations of cold EGF, and Scatchard analysis showed the presence of two classes of EGF binding sites, with K d1 =0·62 0·23 nM and K d2 =53·8 8·2 nM for the high-and low-affinity binding sites respectively. The distribution of EGF binding sites was studied in 42 cases by a single-point assay, in the presence and in the absence of a 100-fold cold EGF excess. A non-parametric distribution of EGF binding sites was observed (median 10·2 fmol/mg membrane protein, range 0·0-332·0). EGF-receptor positivity, defined as EGF binding d10·0 fmol/mg protein, was observed in 23 samples (54·8%), especially in prolactinomas (76·5%, P<0·05 vs other tumors taken together) and in gonadotrope adenomas (62·5%). EGF binding was higher in invasive than in non-invasive adenomas (median: 12·8 vs 0·0 fmol/mg membrane protein, P=0·047), and especially in adenomas invading the sphenoid sinus (median 26·7 fmol/mg membrane protein, P=0·008 vs other adenomas). EGF binding also tended to increase with the grade of supra/extrasellar extension according to Wilson (P=0·15). Sex steroid receptors (SSRs) were simultaneously determined in both cytosolic and nuclear fractions of 31 pituitary adenomas. Estrogen and progesterone receptors were determined by an enzyme-linked immunoassay and androgen receptors by a competitive binding assay with [3 H]methyltrienolone. No correlation could be found between EGF binding and either the gender and gonadal status of the patients, or the expression of SSRs by the adenomas. We conclude that the EGF family of growth factors may play a role in the evolution of a significant subset of human pituitary adenomas, especially in their invasiveness, and that a high EGF binding capacity may represent an additional marker of aggressiveness for these tumors. Sex steroids do not appear to have a significant role in the regulation of EGF binding in vivo in these tumors.

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“…P. Mellon (University of California, San Diego, San Diego, CA) and D. Weiner (University of California, San Francisco, San Francisco, CA). This cell line was grown in DMEM supplemented with 10% fetal bovine serum.For hormone assays, cells were cultured in the presence of 1 nM EGF (Sigma-Aldrich, St. Louis, MO) concentration based on the previous reports by using pituitary (Birman et al, 1987) cells, including GH4C1 cell line (Aanestad et al, 1993). Nerve growth factor (NGF) (Sigma-Aldrich) was chosen as a negative control for EGF actions because these two growth factors use partly overlapping transduction pathways but induce morphologically and biochemically distinct cellular responses both in nonrelated (Huff and Guroff, 1981) and somato-lactotrope (Yoshinaga et al, 1998) cell lines.…”

mentioning

confidence: 99%

Epidermal Growth Factor Triggers an Original, Caspase-independent Pituitary Cell Death with Heterogeneous Phenotype

Fombonne

Reix

Rasolonjanahary

et al. 2004

MBoC

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Programmed cell death (PCD) is physiologically involved in the regulation of cell division and differentiation. It encompasses caspase-dependent mitochondrial and nonmitochondrial pathways. Additional caspase-independent pathways have been characterized in mitochondrial PCDs but remain hypothetical in nonmitochondrial PCDs. Epidermal growth factor (EGF) has been shown to inhibit division of pituitary somato-lactotrope cells occurring in parallel with EGF-mediated differentiation of these precursors into lactotrope cells. We show here that in somato-lactotrope pituitary cell line GH4C1, EGF triggers a PCD characterized by an apoptosis-like DNA fragmentation, insensitivity to broad-range caspase inhibitors, and absence of either cytochrome c or apoptosis-inducing factor release from mitochondria. Dying cells display loose chromatin clustering and numerous cytoplasmic vacuoles, a fraction of which are autophagic, thus conferring a heterogeneous phenotype to this PCD. Moreover, overexpression of cell death inhibitor Bcl-2 prevented not only the EGF-induced PCD but also its prodifferentiation effects, thus pointing to a mechanistic relationship existing between these two phenomena. Overall, the characterized differentiation-linked cell death represents an original form of caspase-independent PCD. The mechanisms underlying this PCD involve combinatorial engagement of discrete death effectors leading to a heterogeneous death phenotype that might be evolutionary related to PCD seen during the differentiation of some unicellular organisms. INTRODUCTIONProgrammed cell death (PCD) is physiologically involved in the control of proliferation/differentiation balance both in the course of development (e.g., organogenesis in mammals) and during the optimization of adult cell/tissue functions (e.g., thymic maturation of T lymphocytes). More recently, PCD has been associated with some pathological processes such as cancer and neurodegeneration. There is currently no consensus on either definition or classification of PCD (Sloviter, 2002;Golstein et al., 2003). The "programmed" character occurs as a hallmark of PCD, but it refers to different aspects of the phenomenon, i.e., to the programmed occurrence of PCD in the course of development (in developmental PCD) or to the programmed succession of morphological and biochemical events (in nondevelopmental PCDs). However, the term programmed is also considered in the sense of "regulated," leading to a broad classification of PCD into apoptosis, necrosis, and autophagy (Golstein et al., 2003).One of the more restraining classifications is based on a particular criterion of the nuclear morphology and divides PCDs into classical apoptosis, apoptosis-like PCD, and necrosis-like PCD characterized by "crescent-like" (type 2), lumpy (type 1), or absence of chromatin condensation, respectively (Jaattela and Tschopp, 2003).Classical apoptosis is the best known phenotypic expression of PCD. It is related to a series of stereotypic morphological and biochemical alterations resulting from the act...

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Epidermal growth factor stimulates the prolactin synthesis and secretion in rat pituitary cells in culture (GH4C1 cells) by increasing the intracellular concentration of free calcium

Cited by 18 publications

References 14 publications

A novel paraptosis pathway involving LEI/L-DNaseII for EGF-induced cell death in somato-lactotrope pituitary cells

A novel paraptosis pathway involving LEI/L-DNaseII for EGF-induced cell death in somato-lactotrope pituitary cells

Epidermal growth factor binding sites in human pituitary macroadenomas

Epidermal Growth Factor Triggers an Original, Caspase-independent Pituitary Cell Death with Heterogeneous Phenotype

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