Thromboxane A2 receptors in prostate carcinoma: expression and its role in regulating cell motility via small GTPase Rho.

Thromboxane A2 receptors in prostate carcinoma: expression and its role in regulating cell motility via small GTPase Rho. Research Abstract Details 

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Thromboxane A2 receptors in prostate carcinoma: expression and its role in regulating cell motility via small GTPase Rho. Abstract Text:

Daotai Nie,Yande Guo,Dianer Yang,Yong Tang,Yakun Chen,Man-Tzu Wang,Alex Zacharek,Yan Qiao,Mingxin Che,Kenneth V Honn,Daotai Nie,Yande Guo,Dianer Yang,Yong Tang,Yakun Chen,Man-Tzu Wang,Alex Zacharek,Yan Qiao,Mingxin Che,Kenneth V Honn,

Thromboxane A(2) (TxA(2)) is a prostanoid formed by thromboxane synthase using the cyclooxygenase product prostaglandin H(2) as the substrate. Previously, increased expression of thromboxane synthase was found in prostate tumors, and tumor cell motility was attenuated by inhibitors of thromboxane synthase. This study was undertaken to elucidate how tumor motility is regulated by TxA(2). Here, we report that human prostate cancer cells express functional receptors for TxA(2) (TP). Ligand binding assay found that PC-3 cells binded to SQ29548, a high-affinity TP antagonist, in a saturable manner with K(d) of 3.64 nmol/L and B(max) of 120.4 fmol per million cells. Treatment of PC-3 cells by U46619, a TP agonist, induced PC-3 cell contraction, which was blocked by pretreatment with the TP antagonist SQ29548 or pinane TxA(2). The migration of prostate cancer cells was significantly inhibited either by sustained activation of TP or by blockade of TP activation, suggesting that TP activation must be tightly controlled during cell migration. Further studies found that small GTPase RhoA was activated by TP activation, and pretreatment of PC-3 cells with Y27632, a Rho kinase (ROCK) inhibitor, blocked U46619-induced cell contraction. A dominant-negative mutant of RhoA also blocked U46619-induced cell contraction. Taken together, the data suggest that TPs are expressed in prostate cancer and activation of TPs regulates prostate cancer cell motility and cytoskeleton reorganization through activation of Rho.

Thromboxane A2 receptors in prostate carcinoma: expression and its role in regulating cell motility via small GTPase Rho. Publishing Authors By Initials

D Nie,Y Guo,D Yang,Y Tang,Y Chen,MT Wang,A Zacharek,Y Qiao,M Che,KV Honn,D Nie,Y Guo,D Yang,Y Tang,Y Chen,MT Wang,A Zacharek,Y Qiao,M Che,KV Honn,

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Thromboxane A2 receptors in prostate carcinoma: expression and its role in regulating cell motility via small GTPase Rho. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Cancer research

VOLUME: 68

Page Numbers: 115-21

Journal Abbreviation: Cancer Res.

ISSN: 1538-7445

DAY: 1

MONTH: Jan

YEAR: 2008

Thromboxane A2 receptors in prostate carcinoma: expression and its role in regulating cell motility via small GTPase Rho. Information

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LANGUAGE: eng

NlmUniqueID: 2984705

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AFFILIATION: Department of Medical Microbiology and Immunology, Southern Illinois University School of Medicine and SimmonsCooper Cancer Institute, Springfield, Illinois 62794, USA. dnie@siumed.edu

Country: United States

AGENCY: United States NCI

GRANT: R01CA114051

ACRONYM: CA

MEDLINETA: Cancer Res

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