AC3 has an Inhibitory Effect on Cell Cycle and Enhances Staurosporine-Induced Apoptosis in Pancreatic Cancer Cells: Participation of R-Smads

Hdl Handle:
http://hdl.handle.net/10675.2/565786
Title:
AC3 has an Inhibitory Effect on Cell Cycle and Enhances Staurosporine-Induced Apoptosis in Pancreatic Cancer Cells: Participation of R-Smads
Authors:
Dains-McGahee, Clayton; Friedman, Emilee; Graves, Sarai; Sabbatini, Maria
Abstract:
Introduction: Adenylyl cyclase (AC) is an enzyme responsible for converting ATP into cAMP. Previously, we found that five AC isoforms are expressed in HPAC and PANC-1. Two of them, AC1 and AC3, were highly expressed in pancreatic tumor tissue. Objective: To silence the expression of AC1 and AC3, in order to determine their participation in the effect of FSK on cell proliferation. Results: After FSK stimulation, there was a slight increase in BrdU incorporation. The lack of AC3 caused a significant increase in FSK-induced BrdU incorporation. FSK on its own had a negligible effect on programmed cell death. The combined effect of FSK along with staurosporine led to an increase in apoptosis. This effect was not seen in cells treated with siRNA AC3. Upon an increase in cAMP, two pathways become active: PKA and Epac. Next, we determined which pathway is activated upon AC1 or AC3 stimulation. Using Western-blotting our data showed that R-Smads were phosphorylated by AC1, whereas CREB was not phosphorylated by either AC1 or AC3. Conclusion: While stimulation of AC by FSK produced a slight increase in BrdU incorporation, the effects of FSK were most exaggerated in the absence of AC3. We hypothesize that AC3 may have an inhibitory effect on cell proliferation of pancreatic cancer cells. While, FSK alone did not modify apoptosis, FSK enhanced staurosporine-induced apoptosis in both cell lines via AC3 activation. In pancreatic cancer cells, CREB is phosphorylated by PKA through a pathway independent of AC1 and AC3, while AC1 phosphorylates R-Smads.
Affiliation:
College of Science and Mathematics
Issue Date:
10-Aug-2015
URI:
http://hdl.handle.net/10675.2/565786
Type:
Presentation
Description:
Poster presentation given at the 2015 CURS Summer Scholars Symposium
Sponsors:
Office of the Provost, VP for Academic and Faculty Affairs, Office of Research
Appears in Collections:
Summer Scholars Program

Full metadata record

DC FieldValue Language
dc.contributor.authorDains-McGahee, Claytonen
dc.contributor.authorFriedman, Emileeen
dc.contributor.authorGraves, Saraien
dc.contributor.authorSabbatini, Mariaen
dc.date.accessioned2015-08-10T22:40:39Zen
dc.date.available2015-08-10T22:40:39Zen
dc.date.issued2015-08-10en
dc.identifier.urihttp://hdl.handle.net/10675.2/565786en
dc.descriptionPoster presentation given at the 2015 CURS Summer Scholars Symposiumen
dc.description.abstractIntroduction: Adenylyl cyclase (AC) is an enzyme responsible for converting ATP into cAMP. Previously, we found that five AC isoforms are expressed in HPAC and PANC-1. Two of them, AC1 and AC3, were highly expressed in pancreatic tumor tissue. Objective: To silence the expression of AC1 and AC3, in order to determine their participation in the effect of FSK on cell proliferation. Results: After FSK stimulation, there was a slight increase in BrdU incorporation. The lack of AC3 caused a significant increase in FSK-induced BrdU incorporation. FSK on its own had a negligible effect on programmed cell death. The combined effect of FSK along with staurosporine led to an increase in apoptosis. This effect was not seen in cells treated with siRNA AC3. Upon an increase in cAMP, two pathways become active: PKA and Epac. Next, we determined which pathway is activated upon AC1 or AC3 stimulation. Using Western-blotting our data showed that R-Smads were phosphorylated by AC1, whereas CREB was not phosphorylated by either AC1 or AC3. Conclusion: While stimulation of AC by FSK produced a slight increase in BrdU incorporation, the effects of FSK were most exaggerated in the absence of AC3. We hypothesize that AC3 may have an inhibitory effect on cell proliferation of pancreatic cancer cells. While, FSK alone did not modify apoptosis, FSK enhanced staurosporine-induced apoptosis in both cell lines via AC3 activation. In pancreatic cancer cells, CREB is phosphorylated by PKA through a pathway independent of AC1 and AC3, while AC1 phosphorylates R-Smads.en
dc.description.sponsorshipOffice of the Provost, VP for Academic and Faculty Affairs, Office of Researchen
dc.subjectPancreatic Canceren
dc.titleAC3 has an Inhibitory Effect on Cell Cycle and Enhances Staurosporine-Induced Apoptosis in Pancreatic Cancer Cells: Participation of R-Smadsen
dc.typePresentationen
dc.contributor.departmentCollege of Science and Mathematicsen
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