Growth factors and human pituitary adenomas

Spada, Anna

doi:10.1530/eje.0.1380255

Cited by 16 publications

(11 citation statements)

References 14 publications

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“…Furthermore, in some cases the overexpression of activating genes (i.e. pituitary tumor transforming gene, hpttg) or loss of tumor suppressor genes (Rb, menin, p53, p27 and p16) was identified (Spada & Lania 2002).…”

Section: Pituitary and Hypothalamic Chemokines In The Development Of mentioning

confidence: 99%

Role of stromal cell-derived factor 1 (SDF1/CXCL12) in regulating anterior pituitary function

Barbieri¹,

Bajetto²,

Porcile³

et al. 2007

Journal of Molecular Endocrinology

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Chemokines are key factors involved in the regulation of immune response, through the activation and control of leukocyte traffic, lymphopoiesis and immune surveillance. However, a large number of chemokines and their receptors are expressed in central nervous system (CNS) cells, either constitutively or induced by inflammatory stimuli, playing a role in many neuropathological processes. Stromal cell-derived factor 1 (SDF1) is a chemokine whose extra-immunological localization and functions have been extensively studied. SDF1 and its receptor CXCR4 were identified in both neurons and glia of many brain areas, including the hypothalamus, as well as at the pituitary level. Importantly, SDF1 and CXCR4 expression is increased in brain tumors in which their activity induced tumor cell proliferation and brain parenchyma invasion. Despite their localization, to date very few reports addressed the role of CXCR4 and SDF1 in the modulation of the hypothalamus/pituitary axis and their possible involvement in the development of pituitary adenomas. In this review, we discuss previous literature data on the role of chemokines in normal and adenomatous pituitary cells, focusing on recent data from our group showing that CXCR4 activation controls proliferation and both prolactin and GH release in the pituitary adenoma cell line GH4C1 through a complex network of intracellular signals. Thus, the SDF1/CXCR4 system together with other chemokinergic ligand-receptor pairs, may represent a novel regulatory pathway for pituitary function and, possibly, be involved in pituitary adenoma development. These lines of evidence suggest that the inhibition of chemokine receptors may represent a novel pharmacological target for the treatment of pituitary adenomas.

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Section: Pituitary and Hypothalamic Chemokines In The Development Of mentioning

confidence: 99%

Role of stromal cell-derived factor 1 (SDF1/CXCL12) in regulating anterior pituitary function

Barbieri¹,

Bajetto²,

Porcile³

et al. 2007

Journal of Molecular Endocrinology

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“…The differentiation of neuronal cells is important for the regular function of the brain. Thus, there is interest in understanding the molecular signaling mechanisms that regulate cell proliferation and differentiation.In a number of cells, most notably of neuronal origin, G s protein-coupled receptors (GsPCR) are key regulators of cell proliferation, differentiation, and survival and play important roles in numerous biological processes such as neoplasia, learning, and memory formation (Kandel, 2001;Spada and Lania, 2002;Wang et al, 2004). The signaling cascades downstream of GsPCRs to regulate these events include activation of adenylyl cyclase, elevation of the intracellular cAMP concentration ([cAMP] i ), and modulation of the extracellular signal-regulated kinase (ERK) 1/2 pathway (Stork, 2003).…”

mentioning

confidence: 99%

Epac Activation Converts cAMP from a Proliferative into a Differentiation Signal in PC12 Cells

Kiermayer

Biondi

Imig

et al. 2005

MBoC

106

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Elevation of the intracellular cAMP concentration ([cAMP]i ) regulates metabolism, cell proliferation, and differentiation and plays roles in memory formation and neoplastic growth. cAMP mediates its effects mainly through activation of protein kinase A (PKA) as well as Epac1 and Epac2, exchange factors activating the small GTPases Rap1 and Rap2. However, how cAMP utilizes these effectors to induce distinct biological responses is unknown. We here studied the specific roles of PKA and Epac in neuroendocrine PC12 cells. In these cells, elevation of [cAMP] i activates extracellular signal-regulated kinase (ERK) 1/2 and induces low-degree neurite outgrowth. The present study showed that specific stimulation of PKA triggered ERK1/2 activation that was considerably more transient than that observed upon simultaneous activation of both PKA and Epac. Unexpectedly, the PKA-specific cAMP analog induced cell proliferation rather than neurite outgrowth. The proliferative signaling pathway activated by the PKA-specific cAMP analog involved activation of the epidermal growth factor receptor and ERK1/2. Activation of Epac appeared to extend the duration of PKA-dependent ERK1/2 activation and converted cAMP from a proliferative into an anti-proliferative, neurite outgrowthpromoting signal. Thus, the present study showed that the outcome of cAMP signaling can depend heavily on the set of cAMP effectors activated. INTRODUCTIONThe normal development of organisms requires a tight coordination between growth and differentiation. Importantly, the regulation of this decision is altered in disease states, most notably in cancer, where growth signals overcome the physiological processes of differentiation. The differentiation of neuronal cells is important for the regular function of the brain. Thus, there is interest in understanding the molecular signaling mechanisms that regulate cell proliferation and differentiation.In a number of cells, most notably of neuronal origin, G s protein-coupled receptors (GsPCR) are key regulators of cell proliferation, differentiation, and survival and play important roles in numerous biological processes such as neoplasia, learning, and memory formation (Kandel, 2001;Spada and Lania, 2002;Wang et al., 2004). The signaling cascades downstream of GsPCRs to regulate these events include activation of adenylyl cyclase, elevation of the intracellular cAMP concentration ([cAMP] i ), and modulation of the extracellular signal-regulated kinase (ERK) 1/2 pathway (Stork, 2003).cAMP binds to and directly activates protein kinase A (PKA) as well as the cAMP binding guanine nucleotide exchange factors Epac1 and -2, which in turn stimulate the small GTPases Rap1 and Rap2. Together, PKA and Epacs appear to mediate the majority of effects of cAMP in mammalian cells (de Rooij et al., 1998;Kawasaki et al., 1998;Bos, 2003). Nevertheless, most work on cAMP-dependent pathways has been centered on the role of PKA. For instance, a role of PKA in memory formation has been verified in numerous in vitro and in vivo studies t...

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“…Jackson et al (24) found that GH4 rat pituitary cells expressed all four FGFRs, and bFGF phosphorylated the tyrosines of FGFR1, FGFR3 and FGFR4, but not FGFR2, and resulted in no signifi cant change in GH4 cell number, which implys that bioactivity of bFGF on GH4 cell is not mitogenic but regulating neuroendocrine. Background researches have proved that bFGF stimulates PRL, GH and TSH secretion, the effect on PRL being the most prominent (25). Basic FGF triggered signaling transduction cascades includes MAPK and so on.…”

Section: Discussionmentioning

confidence: 99%

Basic fibroblast growth factor upregulates expression of growth hormone gene through extracellular signal-regulated kinase 1/2 in GH4 cells

Liu¹,

Luo²,

Chen³

et al. 2013

BLL

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Basic fi broblast growth factor (bFGF) is reported to not only play multifunctions in pituitary differentiation and tumor formation, stimulating cell differentiation or proliferation, also stimulate pituitary to secret prolactin, growth hormone (GH) and thyroid stimulating hormone, although obvious effect on growth hormone only responded to high-dose bFGF. Since it is well documented that both bFGF and GH correlate closely to tumorigenesis, development and metastasis, so it is necessary to reveal the relationship between the cytokines. In the present report we investigated the effect of bFGF on transcription level of GH gene in GH4 rat pituitary cells as well as the regulatory mechanism with real-time reverse transcription polymerase chain reaction and western blotting. We observed a signifi cant expressional increase of GH gene in GH4 cells stimulated by bFGF, meanwhile phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) was also found in the cells. Further investigation unveiled that PD98059, a specifi c inhibitor of ERK1/2 signaling pathway markedly impaired the transcriptional increment of GH gene induced by bFGF in the pituitary cells, which indicates that bFGF upregulates GH gene expression through ERK1/2 signaling pathway in GH4 cells. Results may be helpful to elaborate roles of the two cytokines on tumor (Fig. 3, Ref. 25). Full Text in PDF www.elis.sk.

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Growth factors and human pituitary adenomas

Cited by 16 publications

References 14 publications

Role of stromal cell-derived factor 1 (SDF1/CXCL12) in regulating anterior pituitary function

Role of stromal cell-derived factor 1 (SDF1/CXCL12) in regulating anterior pituitary function

Epac Activation Converts cAMP from a Proliferative into a Differentiation Signal in PC12 Cells

Basic fibroblast growth factor upregulates expression of growth hormone gene through extracellular signal-regulated kinase 1/2 in GH4 cells

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