Regulator of G-protein signaling 5 reduces HeyA8 ovarian cancer cell proliferation and extends survival in a murine tumor model

Molly K. Altman, Duy T. Nguyen, Santosh B. Patel, Jada M. Fambrough, Aaron M. Beedle, William J. Hardman, Mandi M. Murph

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The regulator of G-protein signaling 5 (RGS5) belongs to a family of GTPase activators that terminate signaling cascades initiated by extracellular mediators and G-protein-coupled receptors. RGS5 has an interesting dual biological role. One functional RGS5 role is as a pericyte biomarker influencing the switch to angiogenesis during malignant progression. Its other functional role is to promote apoptosis in hypoxic environments. We set out to clarify the extent to which RGS5 expression regulates tumor progression'whether it plays a pathogenic or protective role in ovarian tumor biology. We thus constructed an inducible gene expression system to achieve RGS5 expression in HeyA8-MDR ovarian cancer cells. Through this we observed that inducible RGS5 expression significantly reduces in vitro BrdU-positive HeyA8-MDR cells, although this did not correlate with a reduction in tumor volume observed using an in vivo mouse model of ovarian cancer. Interestingly, mice bearing RGS5-expressing tumors demonstrated an increase in survival compared with controls, which might be attributed to the vast regions of necrosis observed by pathological examination. Additionally, mice bearing RGS5-expressing tumors were less likely to have ulcerated tumors. Taken together, this data supports the idea that temporal expression and stabilization of RGS5 could be a valuable tactic within the context of a multicomponent approach for modulating tumor progression.

Original languageEnglish (US)
Article number518437
JournalBiochemistry Research International
DOIs
StatePublished - Aug 17 2012

Fingerprint

GTP-Binding Protein Regulators
Cell proliferation
Ovarian Neoplasms
Tumors
Cell Proliferation
Neoplasms
Bearings (structural)
GTP Phosphohydrolase Activators
Pericytes
Bromodeoxyuridine
G-Protein-Coupled Receptors
Tumor Burden
Biomarkers
Necrosis
Gene expression
Apoptosis
Gene Expression
Stabilization
Cells
Switches

ASJC Scopus subject areas

  • Biochemistry

Cite this

Regulator of G-protein signaling 5 reduces HeyA8 ovarian cancer cell proliferation and extends survival in a murine tumor model. / Altman, Molly K.; Nguyen, Duy T.; Patel, Santosh B.; Fambrough, Jada M.; Beedle, Aaron M.; Hardman, William J.; Murph, Mandi M.

In: Biochemistry Research International, 17.08.2012.

Research output: Contribution to journalArticle

Altman, Molly K. ; Nguyen, Duy T. ; Patel, Santosh B. ; Fambrough, Jada M. ; Beedle, Aaron M. ; Hardman, William J. ; Murph, Mandi M. / Regulator of G-protein signaling 5 reduces HeyA8 ovarian cancer cell proliferation and extends survival in a murine tumor model. In: Biochemistry Research International. 2012.
@article{b2691d37c0af45f8abadb26a2ac1da09,
title = "Regulator of G-protein signaling 5 reduces HeyA8 ovarian cancer cell proliferation and extends survival in a murine tumor model",
abstract = "The regulator of G-protein signaling 5 (RGS5) belongs to a family of GTPase activators that terminate signaling cascades initiated by extracellular mediators and G-protein-coupled receptors. RGS5 has an interesting dual biological role. One functional RGS5 role is as a pericyte biomarker influencing the switch to angiogenesis during malignant progression. Its other functional role is to promote apoptosis in hypoxic environments. We set out to clarify the extent to which RGS5 expression regulates tumor progression'whether it plays a pathogenic or protective role in ovarian tumor biology. We thus constructed an inducible gene expression system to achieve RGS5 expression in HeyA8-MDR ovarian cancer cells. Through this we observed that inducible RGS5 expression significantly reduces in vitro BrdU-positive HeyA8-MDR cells, although this did not correlate with a reduction in tumor volume observed using an in vivo mouse model of ovarian cancer. Interestingly, mice bearing RGS5-expressing tumors demonstrated an increase in survival compared with controls, which might be attributed to the vast regions of necrosis observed by pathological examination. Additionally, mice bearing RGS5-expressing tumors were less likely to have ulcerated tumors. Taken together, this data supports the idea that temporal expression and stabilization of RGS5 could be a valuable tactic within the context of a multicomponent approach for modulating tumor progression.",
author = "Altman, {Molly K.} and Nguyen, {Duy T.} and Patel, {Santosh B.} and Fambrough, {Jada M.} and Beedle, {Aaron M.} and Hardman, {William J.} and Murph, {Mandi M.}",
year = "2012",
month = "8",
day = "17",
doi = "10.1155/2012/518437",
language = "English (US)",
journal = "Biochemistry Research International",
issn = "2090-2247",
publisher = "Hindawi Publishing Corporation",

}

TY - JOUR

T1 - Regulator of G-protein signaling 5 reduces HeyA8 ovarian cancer cell proliferation and extends survival in a murine tumor model

AU - Altman, Molly K.

AU - Nguyen, Duy T.

AU - Patel, Santosh B.

AU - Fambrough, Jada M.

AU - Beedle, Aaron M.

AU - Hardman, William J.

AU - Murph, Mandi M.

PY - 2012/8/17

Y1 - 2012/8/17

N2 - The regulator of G-protein signaling 5 (RGS5) belongs to a family of GTPase activators that terminate signaling cascades initiated by extracellular mediators and G-protein-coupled receptors. RGS5 has an interesting dual biological role. One functional RGS5 role is as a pericyte biomarker influencing the switch to angiogenesis during malignant progression. Its other functional role is to promote apoptosis in hypoxic environments. We set out to clarify the extent to which RGS5 expression regulates tumor progression'whether it plays a pathogenic or protective role in ovarian tumor biology. We thus constructed an inducible gene expression system to achieve RGS5 expression in HeyA8-MDR ovarian cancer cells. Through this we observed that inducible RGS5 expression significantly reduces in vitro BrdU-positive HeyA8-MDR cells, although this did not correlate with a reduction in tumor volume observed using an in vivo mouse model of ovarian cancer. Interestingly, mice bearing RGS5-expressing tumors demonstrated an increase in survival compared with controls, which might be attributed to the vast regions of necrosis observed by pathological examination. Additionally, mice bearing RGS5-expressing tumors were less likely to have ulcerated tumors. Taken together, this data supports the idea that temporal expression and stabilization of RGS5 could be a valuable tactic within the context of a multicomponent approach for modulating tumor progression.

AB - The regulator of G-protein signaling 5 (RGS5) belongs to a family of GTPase activators that terminate signaling cascades initiated by extracellular mediators and G-protein-coupled receptors. RGS5 has an interesting dual biological role. One functional RGS5 role is as a pericyte biomarker influencing the switch to angiogenesis during malignant progression. Its other functional role is to promote apoptosis in hypoxic environments. We set out to clarify the extent to which RGS5 expression regulates tumor progression'whether it plays a pathogenic or protective role in ovarian tumor biology. We thus constructed an inducible gene expression system to achieve RGS5 expression in HeyA8-MDR ovarian cancer cells. Through this we observed that inducible RGS5 expression significantly reduces in vitro BrdU-positive HeyA8-MDR cells, although this did not correlate with a reduction in tumor volume observed using an in vivo mouse model of ovarian cancer. Interestingly, mice bearing RGS5-expressing tumors demonstrated an increase in survival compared with controls, which might be attributed to the vast regions of necrosis observed by pathological examination. Additionally, mice bearing RGS5-expressing tumors were less likely to have ulcerated tumors. Taken together, this data supports the idea that temporal expression and stabilization of RGS5 could be a valuable tactic within the context of a multicomponent approach for modulating tumor progression.

UR - http://www.scopus.com/inward/record.url?scp=84864949719&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864949719&partnerID=8YFLogxK

U2 - 10.1155/2012/518437

DO - 10.1155/2012/518437

M3 - Article

C2 - 22792465

AN - SCOPUS:84864949719

JO - Biochemistry Research International

JF - Biochemistry Research International

SN - 2090-2247

M1 - 518437

ER -