Lysophosphatidic acid is a major regulator of growth-regulated oncogene α in ovarian cancer

Zendra Lee, Ramona F. Swaby, Yuewei Liang, Shuangxing Yu, Shuying Liu, Karen H. Lu, Robert C. Bast, Gordon Mills, Xianjun Fang

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Growth-regulated oncogene α (GROα), a member of the chemokine superfamily, is commonly expressed in transformed cells and contributes to angiogenesis and tumorigenesis. Here, we report that increased GROα levels are detected in the plasma and ascites of ovarian cancer patients. Ovarian cancer cell lines in culture express and secrete GROα. However, when they are starved in serum-free medium, ovarian cancer cells ceased producing GROα, suggesting that GROα is not constitutively expressed but rather is produced in response to exogenous growth factors in ovarian cancer cells. The prototype peptide growth factors present in serum such as platelet-derived growth factor, insulin-like growth factor I, and insulin do not stimulate GROα production by ovarian cancer cells. In contrast, lysophosphatidic acid (LPA), a glycerol backbone phospholipid mediator present in serum and ascites of ovarian cancer patients, is a potent inducer of GROα expression in ovarian cancer cell lines. Treatment of ovarian cancer cells with LPA leads to transcriptional activation of the GROα gene promoter and robust accumulation of GROα protein in culture supernatants. The action of LPA on GROα expression is mediated by LPA receptors, particularly the LPA2 receptor in that ectopic expression of these receptors restores the LPA-dependent GROα production in nonresponsive cells. Down-regulation of LPA2 expression by small interfering RNA (siRNA) in ovarian cancer cells desensitizes GROα production in response to LPA. The effect of serum on GROα production is also significantly decreased by siRNA inhibition of LPA2 expression. These studies identify LPA as a primary regulator of GROα expression in ovarian cancer.

Original languageEnglish (US)
Pages (from-to)2740-2748
Number of pages9
JournalCancer Research
Volume66
Issue number5
DOIs
StatePublished - Mar 1 2006
Externally publishedYes

Fingerprint

Oncogenes
Ovarian Neoplasms
Growth
Lysophosphatidic Acid Receptors
lysophosphatidic acid
Ascites
Small Interfering RNA
Intercellular Signaling Peptides and Proteins
Serum
Cell Line
Oncogene Proteins
Platelet-Derived Growth Factor
Serum-Free Culture Media
Insulin-Like Growth Factor I
Chemokines
Glycerol
Transcriptional Activation
Phospholipids
Carcinogenesis
Down-Regulation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Lee, Z., Swaby, R. F., Liang, Y., Yu, S., Liu, S., Lu, K. H., ... Fang, X. (2006). Lysophosphatidic acid is a major regulator of growth-regulated oncogene α in ovarian cancer. Cancer Research, 66(5), 2740-2748. https://doi.org/10.1158/0008-5472.CAN-05-2947

Lysophosphatidic acid is a major regulator of growth-regulated oncogene α in ovarian cancer. / Lee, Zendra; Swaby, Ramona F.; Liang, Yuewei; Yu, Shuangxing; Liu, Shuying; Lu, Karen H.; Bast, Robert C.; Mills, Gordon; Fang, Xianjun.

In: Cancer Research, Vol. 66, No. 5, 01.03.2006, p. 2740-2748.

Research output: Contribution to journalArticle

Lee, Z, Swaby, RF, Liang, Y, Yu, S, Liu, S, Lu, KH, Bast, RC, Mills, G & Fang, X 2006, 'Lysophosphatidic acid is a major regulator of growth-regulated oncogene α in ovarian cancer', Cancer Research, vol. 66, no. 5, pp. 2740-2748. https://doi.org/10.1158/0008-5472.CAN-05-2947
Lee, Zendra ; Swaby, Ramona F. ; Liang, Yuewei ; Yu, Shuangxing ; Liu, Shuying ; Lu, Karen H. ; Bast, Robert C. ; Mills, Gordon ; Fang, Xianjun. / Lysophosphatidic acid is a major regulator of growth-regulated oncogene α in ovarian cancer. In: Cancer Research. 2006 ; Vol. 66, No. 5. pp. 2740-2748.
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