LPA2 (EDG4) mediates Rho-dependent chemotaxis with lower efficacy than LPA1 (EDG2) in breast carcinoma cells.

LPA2 (EDG4) mediates Rho-dependent chemotaxis with lower efficacy than LPA1 (EDG2) in breast carcinoma cells. Research Abstract Details 

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LPA2 (EDG4) mediates Rho-dependent chemotaxis with lower efficacy than LPA1 (EDG2) in breast carcinoma cells. Abstract Text:

Min Chen,L Nicole Towers,Kathleen L O'Connor,

Lysophosphatidic acid (LPA) acts via binding to specific G protein-coupled receptors and has been implicated in the biology of breast cancer. Here, we characterize LPA receptor expression patterns in common established breast cancer cell lines and their contribution to breast cancer cell motility. By measuring expression of the LPA receptors LPA1, LPA2, and LPA3 with real-time quantitative PCR, we show that the breast cancer cell lines tested can be clustered into three main groups: cells that predominantly express LPA1 (BT-549, Hs578T, MDA-MB-157, MDA-MB-231, and T47D), cells that predominantly express LPA2 (BT-20, MCF-7, MDA-MB-453, and MDA-MB-468), and a third group that shows comparable expression level of these two receptors (MDA-MB-175 and MDA-MB-435). LPA3 expression was detected primarily in MDA-MB-157 cells. Using a Transwell chemotaxis assay to monitor dose response, we find that cells predominantly expressing LPA1 have a peak migration rate at 100 nM LPA that drops off dramatically at 1 microM LPA, whereas cells predominantly expressing LPA2 show the peak migration rate at 1 microM LPA, which remains high at 10 microM. Using BT-20 cells, LPA2-specific small interfering RNA, and C3 exotransferase, we demonstrate that LPA2 can mediate LPA-stimulated cell migration and activation of the small GTPase RhoA. Using LPA2 small interfering RNA, exogenous expression of LPA1, and treatment with Ki16425 LPA receptor antagonist in the BT-20 cells, we further find that LPA1 and LPA2 cooperate to promote LPA-stimulated chemotaxis. In summary, our results suggest that the expression of both LPA1 and LPA2 may contribute to chemotaxis and may permit cells to respond optimally to a wider range of LPA concentrations, thus revealing a new aspect of LPA signaling.

LPA2 (EDG4) mediates Rho-dependent chemotaxis with lower efficacy than LPA1 (EDG2) in breast carcinoma cells. Publishing Authors By Initials

M Chen,LN Towers,KL O'Connor,

For similar enzymes and coenzymes: enzymes: hydrolases: acid anhydride hydrolases: gtp phosphohydrolases: gtp-binding proteins: monomeric gtp-binding proteins: rho gtp-binding proteins research abstracts see: enzymes and coenzymes: enzymes: hydrolases: acid anhydride hydrolases: gtp phosphohydrolases: gtp-binding proteins: monomeric gtp-binding proteins: rho gtp-binding proteins research

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LPA2 (EDG4) mediates Rho-dependent chemotaxis with lower efficacy than LPA1 (EDG2) in breast carcinoma cells. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: American journal of physiology. Cell physiology

VOLUME: 292

Page Numbers: C1927-33

Journal Abbreviation: Am. J. Physiol., Cell Physiol.

ISSN: 0363-6143

DAY: 3

MONTH: May

YEAR: 2007

LPA2 (EDG4) mediates Rho-dependent chemotaxis with lower efficacy than LPA1 (EDG2) in breast carcinoma cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 100901225

LPA2 (EDG4) mediates Rho-dependent chemotaxis with lower efficacy than LPA1 (EDG2) in breast carcinoma cells. Keywords Mesh Terms:

KEYWORDS: rho GTP-Binding Proteins

MESH TERMS: metabolism

Chemical & Substance for Abstract: LPA2 (EDG4) mediates Rho-dependent chemotaxis with lower efficacy than LPA1 (EDG2) in breast carcinoma cells. Information

Substance Name: rho GTP-Binding Proteins

Registry Number: EC 3.6.5.2

Grant and Affiliation Information for LPA2 (EDG4) mediates Rho-dependent chemotaxis with lower efficacy than LPA1 (EDG2) in breast carcinoma cells.

AFFILIATION: Department of Surgery, University of Texas Medical Branch, 301 Univ. Blvd., Galveston, TX 77555-0525, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: R21 GM-071928

ACRONYM: GM

MEDLINETA: Am J Physiol Cell Physiol

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