VEGF- and LPA-induced telomerase in human ovarian cancer cells is Sp1-dependent

Yira Bermudez, Hua Yang, Beatriz O. Saunders, Jin Q. Cheng, Santo V. Nicosia, Patricia A. Kruk

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Objective.: Both vascular endothelial growth factor (VEGF) and lysophosphatidic acid (LPA) are secreted by ovarian cancer cells and are known to promote cancer cell growth though the exact mechanism(s) are not completely understood. Since telomerase, a ribonucleprotein expressed in 95% of ovarian cancers, plays an important role in cellular immortalization, growth, and tumor progression, we examined whether telomerase is a molecular target of LPA and VEGF in ovarian cancer. Methods.: Telomerase-positive ovarian carcinoma cell lines PA-1, SW 626, and one telomerase-negative, non-tumorigenic SV40 large-T antigen-transfected human ovarian surface epithelial (IOSE) cell line, FHIOSE 118, derived from normal ovarian surface epithelium were cultured with and without VEGF and LPA for 4 h and 24 h, respectively. Telomerase PCR-ELISA, RT-PCR, VEGF ELISA and luciferase assays were performed to determine the effect of VEGF and LPA on telomerase activity in ovarian cancer cells. Western blot analyses were used to examine the signaling pathway involved in telomerase regulation by VEGF and LPA. Results.: We report that: (1) both VEGF and LPA upregulate telomerase activity; (2) LPA induction of telomerase activity is VEGF-dependent; (3) VEGF and LPA induction of telomerase activity is ERK 1/2-dependent; and (4) Sp1 binding sites within the proximal 976- to 378-bp regions of the hTERT promoter are essential for VEGF- and LPA-induced hTERT promoter activity. Conclusion.: Consequently, these data show the novel finding that VEGF can regulate telomerase activity in non-endothelial cells and that telomerase appears to be a novel molecular target of LPA.

Original languageEnglish (US)
Pages (from-to)526-537
Number of pages12
JournalGynecologic Oncology
Volume106
Issue number3
DOIs
StatePublished - Sep 2007
Externally publishedYes

Fingerprint

Telomerase
Ovarian Neoplasms
Vascular Endothelial Growth Factor A
lysophosphatidic acid
Enzyme-Linked Immunosorbent Assay
Polyomavirus Transforming Antigens
Cell Line
Polymerase Chain Reaction
Viral Tumor Antigens
Growth
Luciferases
Genetic Promoter Regions
Neoplasms
Up-Regulation
Epithelium
Western Blotting
Epithelial Cells
Binding Sites

Keywords

  • hTERT
  • LPA
  • MAPK
  • Ovarian cancer
  • Sp1
  • Telomerase
  • VEGF

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

VEGF- and LPA-induced telomerase in human ovarian cancer cells is Sp1-dependent. / Bermudez, Yira; Yang, Hua; Saunders, Beatriz O.; Cheng, Jin Q.; Nicosia, Santo V.; Kruk, Patricia A.

In: Gynecologic Oncology, Vol. 106, No. 3, 09.2007, p. 526-537.

Research output: Contribution to journalArticle

Bermudez, Yira ; Yang, Hua ; Saunders, Beatriz O. ; Cheng, Jin Q. ; Nicosia, Santo V. ; Kruk, Patricia A. / VEGF- and LPA-induced telomerase in human ovarian cancer cells is Sp1-dependent. In: Gynecologic Oncology. 2007 ; Vol. 106, No. 3. pp. 526-537.
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AU - Yang, Hua

AU - Saunders, Beatriz O.

AU - Cheng, Jin Q.

AU - Nicosia, Santo V.

AU - Kruk, Patricia A.

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