Ghrelin enhances the growth of cultured human adrenal zona glomerulosa cells by exerting MAPK-mediated proliferogenic and antiapoptotic effects

Mazzocchi, Giuseppina; Neri, Giuliano; Ruciński, Marcin; Rebuffat, Piera; Spinazzi, Raffaella; Malendowicz, Ludwik K.; Nussdorfer, Gastone G.

doi:10.1016/j.peptides.2004.05.011

Cited by 63 publications

(39 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanism underlying ghrelin-induced proliferation in breast cancer is unknown, although it is likely to act by stimulating the mitogen-activated protein kinase pathway, as demonstrated in our own studies in the prostate and in similar studies in HepG2 cells (Murata et al 2002), cardiomyocytes (Baldanzi et al 2002), adrenal cells (Andreis et al 2003, Mazzocchi et al 2004), 3T3-L1 adipocytes (Kim et al 2004) and rodent GH3 cells (Nanzer et al 2004). Alternatively, ghrelin could act by stimulating GH secretion from the breast epithelium.…”

Section: Discussionmentioning

confidence: 66%

“…At the functional level, n-octanoylated ghrelin treatment increases the rate of proliferation in a number of cell lines, including human prostate cancer (Jeffery et al 2002), HepG2 hepatoma (Murata et al 2002) and pancreatic adenocarcinoma cancer cell lines (Duxbury et al 2003), rodent pituitary tumour cells (Nanzer et al 2004), as well as some normal cell lines and primary cell cultures (Pettersson et al 2002, Andreis et al 2003, Kim et al 2004, Mazzocchi et al 2004, Zhang et al 2004b, Maccarinelli et al 2005. There is evidence to suggest that a similar system could exist in female hormone-dependent cancers, such as breast cancer.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Expression and function of the ghrelin axis, including a novel preproghrelin isoform, in human breast cancer tissues and cell lines

Jeffery

Murray²,

Yeh³

et al. 2005

Endocr Relat Cancer

111

View full text Add to dashboard Cite

While oestrogen, progesterone and growth factors, including growth hormone (GH), are clearly implicated in the pathogenesis of breast cancer, there is now evidence that the newly described ghrelin axis is also involved. The aims of this study were to investigate the expression of the ghrelin axis in breast cancer tissues and cell lines and to examine the effect of ghrelin on breast cancer cell proliferation in vitro. Ghrelin and its functional receptor, the growth hormone secretagogue receptor (GHSR) type 1a, were expressed in normal breast tissue and breast cancer specimens and cell lines. In contrast, the truncated GHSR type 1b isoform was exclusively expressed in breast carcinoma, suggesting that it has potential as a diagnostic marker. Ghrelin treatment significantly increases the proliferation of the MDA-MB-435 and MDA-MB-231 breast cancer cell lines in vitro. In addition, we have described the expression of a human preproghrelin isoform, exon 3-deleted preproghrelin, which encodes mature ghrelin plus a novel C-terminal peptide. Quantitative RT-PCR was used to demonstrate that this mRNA isoform is highly expressed in the MDA-MB-435 metastatic breast cancer cell line relative to the benign MCF-10A breast epithelial cell line. The unique C-terminal peptide of exon 3-deleted preproghrelin is expressed in the glandular epithelium of breast cancer tissues, with high-grade carcinoma exhibiting the strongest immunoreactivity. The data presented here suggest that components of the ghrelin axis may represent novel markers for breast cancer and potential therapeutic targets.

show abstract

Section: Discussionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Expression and function of the ghrelin axis, including a novel preproghrelin isoform, in human breast cancer tissues and cell lines

Jeffery

Murray²,

Yeh³

et al. 2005

Endocr Relat Cancer

111

View full text Add to dashboard Cite

show abstract

“…By contrast, the control of cell size in zona fasciculata cells has been attributed to the phosphoinositol-3-kinase pathway (Lawlor et al 2002). The effects of ERK1/2 on cell number can be exerted by different mechanisms: A) an induction of cell proliferation , Andreis et al 2000, 2003, Whitworth et al 2002, Mazzocchi et al 2004, Ho et al 2005, Ferreira et al 2007, B) by blockade of apoptosis (Mazzocchi et al 2004, Edwin & Patel 2008 or C) by promoting cell survival (Ziegler et al 2006). Although it is widely accepted that ERK activity is required for cell proliferation and mitosis (Chambard et al 2007), it has been shown recently that too high ERK1/2 activity also can block the entry into mitosis (Rahmouni et al 2006).…”

Section: Intracellular Control Of Adrenal Growthmentioning

confidence: 99%

“…The permanent perception of diverse factors affecting adrenal growth and function argues in favor of one common intracellular target, which coordinates and integrates the different stimuli and which further represents a potent effector of central cellular responses like proliferation, survival, apoptosis, or differentiation. As a potential candidate for an intracellular target in adrenal cells extracellular signal regulated kinases 1/2 (ERK1/2) have been demonstrated to affect cell proliferation , Andreis et al 2000, Lepique et al 2000, Lotfi et al 2000, Whitworth et al 2002, Ferreira et al 2007, apoptosis (Mazzocchi et al 2004, Edwin & Patel 2008 cell survival (Ziegler et al 2006), cell migration (Ho et al 2001(Ho et al , 2005, or synthesis and secretion of cortical ( Wu et al 2002, Otis et al 2005, Kempná et al 2007, Chang et al 2008 or medullary hormones (Cox & Parsons 1997, Shibuya et al 2002. Thus, in fact, ERK1/2 have the potential and format to represent such common targets with multiple biological effects in the adrenal gland as proposed before (Chabre et al 1995).…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of adrenal gland growth: signal integration by extracellular signal regulated kinases1/2

Hoeflich¹,

Bielohuby²

2008

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

The adrenal gland influences a multitude of processes during stress response, but also potently affects the immune system, glucose metabolism, electrolyte or water homeostasis, and cardiovascular functions. According to the present understanding, the adrenal cortex is tightly controlled by the hypothalamic-pituitary-adrenal axis. This axis involves hypothalamic CRH and pituitary ACTH which determine processes of adrenocortical growth and function. However, control of the adrenal gland comprises a plethora of additional endogenous or exogenous factors. Among those are diverse hormones, psychosocial parameters, physiological stress, secondary plant products, or even environmental pollutants. In the present review, we summarize the current view of endocrine growth control in the adrenal gland. We then discuss intracellular mechanisms of adrenal growth control and focus on extracellular signal regulated kinases 1/2 ( ERK1/2), which have been demonstrated to be controlled by not only ACTH or angiotensin II, but also by a large number of additional effectors. On the basis of these multiple exogenous or endogenous factors which impact on the adrenal gland through ERK1/2 activity, we speculate on a mechanism by which ERK1/2 act as a central integrative growth regulatory elements in the adrenal gland.

show abstract

“…Numerous lines of evidence indicate that ghrelin and its receptors are expressed in the human and rat adrenal cortex (8)(9)(10)(11)(12)(13). Consistent findings show that ghrelin does not affect adrenal steroid-hormone secretion (8,10,11,13), but is able to enhance proliferative activity of cultured human and rat zona glomerulosa cells (10,13). Ghrelin was also found to decrease apoptotic deletion rate in cultured human adrenocortical cells (13), but to increase it in human aldosteronomas and adrenocortical carcinomaderived cell lines NCI-H295 and SW-13 (14).…”

Section: Introductionmentioning

confidence: 99%

Age-dependent decrease in the ghrelin gene expression in the human adrenal cortex: A real-time PCR study

Carraro

Albertin²,

Aragona³

et al. 2006

Int J Mol Med

Self Cite

View full text Add to dashboard Cite

Abstract. Numerous lines of evidence indicate that ghrelin, an endogenous ligand of the growth hormone-secretagogue receptor, is expressed in the human and rat adrenal cortex. In this study, we examined whether ghrelin gene expression undergoes changes in the human adrenal cortex during aging. Semi-quantitative real-time reverse transcription-polymerase chain reaction demonstrated a highly significant negative correlation between ghrelin mRNA and age in adrenal cortexes of 27 patients (aged from 33 to 82 years), who underwent unilateral adrenalectomy/nephrectomy for kidney cancer. No significant differences in the level of adrenal ghrelin expression were observed between males and females. Since it has been previously shown that ghrelin exerts a marked growthstimulating action on cultured adrenocortical cells, we hypothesize that the down-regulation of ghrelin gene transcription in adrenals could be associated with the reported decrease in adrenal DNA synthesis and mitogenic activity during aging.

show abstract

Ghrelin enhances the growth of cultured human adrenal zona glomerulosa cells by exerting MAPK-mediated proliferogenic and antiapoptotic effects

Cited by 63 publications

References 52 publications

Expression and function of the ghrelin axis, including a novel preproghrelin isoform, in human breast cancer tissues and cell lines

Expression and function of the ghrelin axis, including a novel preproghrelin isoform, in human breast cancer tissues and cell lines

Mechanisms of adrenal gland growth: signal integration by extracellular signal regulated kinases1/2

Age-dependent decrease in the ghrelin gene expression in the human adrenal cortex: A real-time PCR study

Contact Info

Product

Resources

About