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Mitogen-activated protein kinases in normal and (pre)neoplastic ovarian surface epithelium.

Choi KC, Auersperg N, Leung PC - Reprod. Biol. Endocrinol. (2003)

Bottom Line: Mitogen-activated protein kinases (MAPKs) are a group of serine/threonine kinases which are activated in response to a diverse array of extracellular stimuli and mediate signal transduction from the cell surface to the nucleus.It has been demonstrated that MAPKs are activated by external stimuli including chemotherapeutic agents, growth factors and reproductive hormones in ovarian surface epithelial cells.Thus, the MAPK signaling pathway may play an important role in the regulation of proliferation, survival and apoptosis in response to these external stimuli in ovarian cancer.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Obstetrics and Gynaecology, BC Children's and Women's Hospital, University of British Columbia, Vancouver, British Columbia, Canada V6H 3V5. kchoi@cw.bc.ca

ABSTRACT
Mitogen-activated protein kinases (MAPKs) are a group of serine/threonine kinases which are activated in response to a diverse array of extracellular stimuli and mediate signal transduction from the cell surface to the nucleus. It has been demonstrated that MAPKs are activated by external stimuli including chemotherapeutic agents, growth factors and reproductive hormones in ovarian surface epithelial cells. Thus, the MAPK signaling pathway may play an important role in the regulation of proliferation, survival and apoptosis in response to these external stimuli in ovarian cancer. In this article, an activation of the MAPK signaling cascade by several key reproductive hormones and growth factors in epithelial ovarian cancer is reviewed.

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Effect of ATP on ERK-1/-2 (p44/p42) and Elk-1 in the absence or presence of PD98059 and staurosporin. To examine the role of ATP on MAPKs in IOSE-29, the cells were pretreated with 50 μM PD98059 or 0.1 μM staurosporin for 30 min, followed by treatment with 100 μM ATP for 10 min. The P-MAPK normalized by T-MAPK was analyzed by immunoblot analysis, and Elk-1, a downstream pathway of ERK-1/-2, was measured by in vitro MAPK assay, respectively. [Reproduced, permission with, from: Choi K-C, Tai C-J, Tzeng C-R, Auersperg N, Leung PC; "Adenosine triphosphate (ATP) activates mitogen-activated protein kinases (MAPKs) in neoplastic ovarian surface epithelium (OSE) cells" in: Biol Reprod 2003, 68: 309–315. Copyright from Society for the Study of Reproduction]
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Figure 5: Effect of ATP on ERK-1/-2 (p44/p42) and Elk-1 in the absence or presence of PD98059 and staurosporin. To examine the role of ATP on MAPKs in IOSE-29, the cells were pretreated with 50 μM PD98059 or 0.1 μM staurosporin for 30 min, followed by treatment with 100 μM ATP for 10 min. The P-MAPK normalized by T-MAPK was analyzed by immunoblot analysis, and Elk-1, a downstream pathway of ERK-1/-2, was measured by in vitro MAPK assay, respectively. [Reproduced, permission with, from: Choi K-C, Tai C-J, Tzeng C-R, Auersperg N, Leung PC; "Adenosine triphosphate (ATP) activates mitogen-activated protein kinases (MAPKs) in neoplastic ovarian surface epithelium (OSE) cells" in: Biol Reprod 2003, 68: 309–315. Copyright from Society for the Study of Reproduction]

Mentions: Similar to FSH, adenosine triphosphate (ATP) has been implicated in the regulation of cell proliferation and activation of MAPK pathway in ovarian cancer cells. ATP binds to heterotrimeric G protein-coupled P2 purinoceptors and extracellular ATP has been suggested to play a role in cellular proliferation and intracellular calcium concentrations (Ca2+) in ovarian cancer cells [19,20]. Our recent results indicated that treatment with ATP resulted in an activation of ERK-1/-2 in IOSE-29 cell line as seen Fig. 5[21]. The stimulatory effect of ATP in the cellular proliferation and MAPK activation was completely abolished in the presence of PD98059 and staurosporin (a PKC inhibitor), suggesting that the growth stimulatory effect of ATP is mediated via PKC-dependent MAPK activation in pre-neoplastic OSE cells (Fig. 5). Treatment with ATP resulted in substantial phosphorylation of Elk-1, further implicating the MAPK cascade in the growth stimulatory effect of ATP in pre-neoplastic OSE cells [21].


Mitogen-activated protein kinases in normal and (pre)neoplastic ovarian surface epithelium.

Choi KC, Auersperg N, Leung PC - Reprod. Biol. Endocrinol. (2003)

Effect of ATP on ERK-1/-2 (p44/p42) and Elk-1 in the absence or presence of PD98059 and staurosporin. To examine the role of ATP on MAPKs in IOSE-29, the cells were pretreated with 50 μM PD98059 or 0.1 μM staurosporin for 30 min, followed by treatment with 100 μM ATP for 10 min. The P-MAPK normalized by T-MAPK was analyzed by immunoblot analysis, and Elk-1, a downstream pathway of ERK-1/-2, was measured by in vitro MAPK assay, respectively. [Reproduced, permission with, from: Choi K-C, Tai C-J, Tzeng C-R, Auersperg N, Leung PC; "Adenosine triphosphate (ATP) activates mitogen-activated protein kinases (MAPKs) in neoplastic ovarian surface epithelium (OSE) cells" in: Biol Reprod 2003, 68: 309–315. Copyright from Society for the Study of Reproduction]
© Copyright Policy
Related In: Results  -  Collection

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Figure 5: Effect of ATP on ERK-1/-2 (p44/p42) and Elk-1 in the absence or presence of PD98059 and staurosporin. To examine the role of ATP on MAPKs in IOSE-29, the cells were pretreated with 50 μM PD98059 or 0.1 μM staurosporin for 30 min, followed by treatment with 100 μM ATP for 10 min. The P-MAPK normalized by T-MAPK was analyzed by immunoblot analysis, and Elk-1, a downstream pathway of ERK-1/-2, was measured by in vitro MAPK assay, respectively. [Reproduced, permission with, from: Choi K-C, Tai C-J, Tzeng C-R, Auersperg N, Leung PC; "Adenosine triphosphate (ATP) activates mitogen-activated protein kinases (MAPKs) in neoplastic ovarian surface epithelium (OSE) cells" in: Biol Reprod 2003, 68: 309–315. Copyright from Society for the Study of Reproduction]
Mentions: Similar to FSH, adenosine triphosphate (ATP) has been implicated in the regulation of cell proliferation and activation of MAPK pathway in ovarian cancer cells. ATP binds to heterotrimeric G protein-coupled P2 purinoceptors and extracellular ATP has been suggested to play a role in cellular proliferation and intracellular calcium concentrations (Ca2+) in ovarian cancer cells [19,20]. Our recent results indicated that treatment with ATP resulted in an activation of ERK-1/-2 in IOSE-29 cell line as seen Fig. 5[21]. The stimulatory effect of ATP in the cellular proliferation and MAPK activation was completely abolished in the presence of PD98059 and staurosporin (a PKC inhibitor), suggesting that the growth stimulatory effect of ATP is mediated via PKC-dependent MAPK activation in pre-neoplastic OSE cells (Fig. 5). Treatment with ATP resulted in substantial phosphorylation of Elk-1, further implicating the MAPK cascade in the growth stimulatory effect of ATP in pre-neoplastic OSE cells [21].

Bottom Line: Mitogen-activated protein kinases (MAPKs) are a group of serine/threonine kinases which are activated in response to a diverse array of extracellular stimuli and mediate signal transduction from the cell surface to the nucleus.It has been demonstrated that MAPKs are activated by external stimuli including chemotherapeutic agents, growth factors and reproductive hormones in ovarian surface epithelial cells.Thus, the MAPK signaling pathway may play an important role in the regulation of proliferation, survival and apoptosis in response to these external stimuli in ovarian cancer.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Obstetrics and Gynaecology, BC Children's and Women's Hospital, University of British Columbia, Vancouver, British Columbia, Canada V6H 3V5. kchoi@cw.bc.ca

ABSTRACT
Mitogen-activated protein kinases (MAPKs) are a group of serine/threonine kinases which are activated in response to a diverse array of extracellular stimuli and mediate signal transduction from the cell surface to the nucleus. It has been demonstrated that MAPKs are activated by external stimuli including chemotherapeutic agents, growth factors and reproductive hormones in ovarian surface epithelial cells. Thus, the MAPK signaling pathway may play an important role in the regulation of proliferation, survival and apoptosis in response to these external stimuli in ovarian cancer. In this article, an activation of the MAPK signaling cascade by several key reproductive hormones and growth factors in epithelial ovarian cancer is reviewed.

Show MeSH
Related in: MedlinePlus