Phosphatidylinositol 3-kinase-dependent, MEK-  independent proliferation in response to CaR activation

Bilderback, Timothy R.; Lee, Fred; Auersperg, Nelly; Rodland, Karin D.

doi:10.1152/ajpcell.00437.2001

Cited by 29 publications

(15 citation statements)

References 28 publications

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“…Our observation that the ERK/MAP kinase pathway is important for the induction of OSE cell growth is supported by previous studies using the MEK inhibitor PD98059 (Bilderback et al 2002). The data presented here is also consistent with a previous report demonstrating the role of ERK in HGF-induced human OSE cell growth and further demonstrates that IGF-I and hCG also induce OSE cell growth via the ERK pathway.…”

Section: Discussionsupporting

confidence: 93%

“…The data presented here is also consistent with a previous report demonstrating the role of ERK in HGF-induced human OSE cell growth and further demonstrates that IGF-I and hCG also induce OSE cell growth via the ERK pathway. Other signalling pathways that are important to maintain OSE cell growth and/or survival include the Akt/ phosphoinositide 3-kinase pathway (Bilderback et al 2002); stimulation of the Akt/phosphoinositide 3-kinase pathway by IGF-I, under the control of hCG, induces cell survival (Kuroda et al 2001).…”

Section: Discussionmentioning

confidence: 99%

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Anti-inflammatory and proliferative responses in human and ovine ovarian surface epithelial cells

Gubbay

Guo²,

Rae³

et al. 2004

Reproduction

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The majority of ovarian cancers (> 90%) are believed to derive from the ovarian surface epithelium (OSE); a single layer covering the entire surface of the ovary. At ovulation, the OSE cell layer undergoes an inflammatory response, involving cell death and growth, in order to overcome ovarian surface rupture. Abnormalities during these processes are believed to contribute to the development of tumours. Using primary cultures of OSE cells, we have compared anti-inflammatory and proliferative responses directly between human and ovine OSE cells to further establish the use of ovine OSE cells as a suitable model system for the study of human OSE cells. In order to compare effects of inflammatory stimulation, expression and activity of 11bhydroxysteroid dehydrogenase (11bHSD) type 1 was measured in OSE cells in response to interleukin (IL)-1a. As previously identified in human OSE cells, treatment of ovine OSE cells with IL-1a stimulated a concomitant increase of 11bHSD type 1 mRNA (31-fold; P < 0.05) and oxoreductase activity, indicating an increased production of antiinflammatory cortisol. To compare the growth of human and ovine OSE cells, OSE cell number was measured in response to treatment with gonadotropins or growth factors. In the presence of FSH, LH or human chorionic gonadotropin (hCG), ovine and human OSE cell growth was similarly stimulated > 1.2-fold (P < 0.05). In the presence of connective tissue growth factor (CTGF) and more significantly insulin growth factor I (IGF-I), human and ovine OSE cell growth was also similarly stimulated >1.2-fold (P < 0.05) and > 1.5-fold (P < 0.01), respectively. The induction of both human and ovine OSE cell growth by IGF-I or hCG was further shown to be dependent on activation of the MAP kinase/extracellular-signal-regulated kinase (ERK) pathway. Stimulation of ovine OSE cell growth by hepatocyte growth factor (HGF) was similarly shown to be ERK-dependent; however, for human OSE cells, HGF only mildly stimulated ERK phosphorylation and failed to stimulate OSE cell growth. The demonstration that human and ovine OSE cells share similarities at the level of cell signalling, gene expression and cellular growth supports the use of ovine OSE cells as a suitable model for the study of human OSE cells.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory and proliferative responses in human and ovine ovarian surface epithelial cells

Gubbay

Guo²,

Rae³

et al. 2004

Reproduction

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“…Calcium levels are important for signalling and growth in OSE cells, with increased proliferation being seen in response to elevated calcium in vitro (McNeil et al 1998, Hobson et al 2000, Bilderback et al 2002, Wright et al 2002. This effect has been shown to be mediated by ERK1/2 (Hobson et al 2000), PI3K Endocrine-Related Cancer (2010) 17 335-349 www.endocrinology-journals.org (Bilderback et al 2002) and the calcium-sensing receptor CaR (Hobson et al 2003). We have shown that FSH-and LH-induced ERK1/2 activation in EOC cell lines is dependent on both extra-and intracellular calcium.…”

Section: Discussionmentioning

confidence: 99%

Gonadotropin-induced ovarian cancer cell migration and proliferation require extracellular signal-regulated kinase 1/2 activation regulated by calcium and protein kinase Cδ

Mertens‐Walker¹,

Bolitho²,

Baxter³

et al. 2010

Endocrine-Related Cancer

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The gonadotropin hypothesis proposes that elevated serum gonadotropin levels may increase the risk of epithelial ovarian cancer (EOC). We have studied the effect of treating EOC cell lines (OV207 and OVCAR-3) with FSH or LH. Both gonadotropins activated the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK1/2) pathway and increased cell migration that was inhibited by the MAPK 1 inhibitor PD98059. Both extra-and intracellular calcium ion signalling were implicated in gonadotropin-induced ERK1/2 activation as treatment with either the calcium chelator EGTA or an inhibitor of intracellular calcium release, dantrolene, inhibited gonadotropin-induced ERK1/2 activation. Verapamil was also inhibitory, indicating that gonadotropins activate calcium influx via L-type voltage-dependent calcium channels. The cAMP/protein kinase A (PKA) pathway was not involved in the mediation of gonadotropin action in these cells as gonadotropins did not increase intracellular cAMP formation and inhibition of PKA did not affect gonadotropin-induced phosphorylation of ERK1/2. Activation of ERK1/2 was inhibited by the protein kinase C (PKC) inhibitor GF 109203X as well as by the PKCd inhibitor rottlerin, and downregulation of PKCd was inhibited by small interfering RNA (siRNA), highlighting the importance of PKCd in the gonadotropin signalling cascade. Furthermore, in addition to inhibition by PD98059, gonadotropin-induced ovarian cancer cell migration was also inhibited by verapamil, GF 109203X and rottlerin. Similarly, gonadotropin-induced proliferation was inhibited by PD98059, verapamil, GF 109203X and PKCd siRNA. Taken together, these results demonstrate that gonadotropins induce both ovarian cancer cell migration and proliferation by activation of ERK1/2 signalling in a calcium-and PKCd-dependent manner.

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“…Depending on cell-specific coupling to appropriate G-proteins, activation of the CaR by elevated extracellular Ca 2 þ reduces the rate of cellular proliferation, as seen in human colon carcinoma (Kallay et al, 2003;Chakrabarty et al, 2005) or ovarian surface epithelial cells (Bilderback et al, 2002), but may also stimulate cell growth, as seen in malignant Leydig cells , and protect from apoptosis, for example, in prostate cancer cells (Lin et al, 1998).…”

Section: Cancermentioning

confidence: 99%

Vitamin D and calcium insufficiency-related chronic diseases: molecular and cellular pathophysiology

Peterlik¹,

Cross²

2009

Eur J Clin Nutr

104

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A compromised vitamin D status, characterized by low 25-hydroxyvitamin D (25-(OH)D) serum levels, and a nutritional calcium deficit are widely encountered in European and North American countries, independent of age or gender. Both conditions are linked to the pathogenesis of many degenerative, malignant, inflammatory and metabolic diseases. Studies on tissue-specific expression and activity of vitamin D metabolizing enzymes, 25-(OH)D-1a-hydroxylase and 25-(OH)D-24-hydroxylase, and of the extracellular calcium-sensing receptor (CaR) have led to the understanding of how, in non-renal tissues and cellular systems, locally produced 1,25-dihydroxyvitamin D 3 (1,25-(OH) 2 D 3 ) and extracellular Ca 2 þ act jointly as key regulators of cellular proliferation, differentiation and function. Impairment of cooperative signalling from the 1,25-(OH) 2 D 3 -activated vitamin D receptor (VDR) and from the CaR in vitamin D and calcium insufficiency causes cellular dysfunction in many organs and biological systems, and, therefore, increases the risk of diseases, particularly of osteoporosis, colorectal and breast cancer, inflammatory bowel disease, insulin-dependent diabetes mellitus type I, metabolic syndrome, diabetes mellitus type II, hypertension and cardiovascular disease. Understanding the underlying molecular and cellular processes provides a rationale for advocating adequate intake of vitamin D and calcium in all populations, thereby preventing many chronic diseases worldwide.

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Phosphatidylinositol 3-kinase-dependent, MEK- independent proliferation in response to CaR activation

Cited by 29 publications

References 28 publications

Anti-inflammatory and proliferative responses in human and ovine ovarian surface epithelial cells

Anti-inflammatory and proliferative responses in human and ovine ovarian surface epithelial cells

Gonadotropin-induced ovarian cancer cell migration and proliferation require extracellular signal-regulated kinase 1/2 activation regulated by calcium and protein kinase Cδ

Vitamin D and calcium insufficiency-related chronic diseases: molecular and cellular pathophysiology

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