4-HPR modulates gene expression in ovarian cells

Molly Brewer, Nathaniel D. Kirkpatrick, J. Taylor Wharton, Jian Wang, Kenneth D Hatch, Nelly Auersperg, Urs Utzinger, David Gershenson, Robert Bast, Changping Zou

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Ovarian cancer has a high rate of recurrence and subsequent mortality following chemotherapy despite intense efforts to improve treatment outcomes. Recent trials have suggested that retinoids, especially 4-(N-hydroxyphenyl) retinamide (4-HPR), play an important role as a chemopreventive agent and are currently being used in clinical trials for ovarian cancer chemoprevention as well as treatment. This study examines the mechanism of its activity in premalignant and cancer cells. We investigated the modulation of gene expression by 4-HPR in immortalized ovarian surface epithelial (IOSE) cells and ovarian cancer (OVCA433) cells with DNA microarray. Real time RT-PCR and western blotting were used to confirm the microarray results and metabolic changes were examined with optical fluorescence spectroscopy. 4-HPR resulted in an up-regulation of expression of proapoptotic genes and mitochondrial uncoupling protein in OVCA433 cells and modulation of the RXR receptors in IOSE cells, and down-regulation of mutant BRCA genes in both IOSE and OVCA433 cells. 4-HPR had a larger effect on the redox in the 433 cells compared to IOSE. These findings suggest that 4-HPR acts through different mechanisms in premalignant ovarian surface cells and cancer cells, with a preventive effect in premalignant cells and a treatment effect in cancer cells.

Original languageEnglish (US)
Pages (from-to)1005-1013
Number of pages9
JournalInternational Journal of Cancer
Volume119
Issue number5
DOIs
StatePublished - Sep 1 2006

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Gene Expression
Epithelial Cells
Ovarian Neoplasms
Neoplasms
retinamide
Fluorescence Spectrometry
Retinoids
Chemoprevention
Oligonucleotide Array Sequence Analysis
Oxidation-Reduction
Real-Time Polymerase Chain Reaction
Up-Regulation
Down-Regulation
Western Blotting
Clinical Trials
Recurrence
Drug Therapy
Mortality
Therapeutics
Genes

Keywords

  • 4-HPR
  • Apoptosis
  • Ovarian cancer cells
  • Retinoids

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Brewer, M., Kirkpatrick, N. D., Wharton, J. T., Wang, J., Hatch, K. D., Auersperg, N., ... Zou, C. (2006). 4-HPR modulates gene expression in ovarian cells. International Journal of Cancer, 119(5), 1005-1013. https://doi.org/10.1002/ijc.21797

4-HPR modulates gene expression in ovarian cells. / Brewer, Molly; Kirkpatrick, Nathaniel D.; Wharton, J. Taylor; Wang, Jian; Hatch, Kenneth D; Auersperg, Nelly; Utzinger, Urs; Gershenson, David; Bast, Robert; Zou, Changping.

In: International Journal of Cancer, Vol. 119, No. 5, 01.09.2006, p. 1005-1013.

Research output: Contribution to journalArticle

Brewer, M, Kirkpatrick, ND, Wharton, JT, Wang, J, Hatch, KD, Auersperg, N, Utzinger, U, Gershenson, D, Bast, R & Zou, C 2006, '4-HPR modulates gene expression in ovarian cells', International Journal of Cancer, vol. 119, no. 5, pp. 1005-1013. https://doi.org/10.1002/ijc.21797
Brewer M, Kirkpatrick ND, Wharton JT, Wang J, Hatch KD, Auersperg N et al. 4-HPR modulates gene expression in ovarian cells. International Journal of Cancer. 2006 Sep 1;119(5):1005-1013. https://doi.org/10.1002/ijc.21797
Brewer, Molly ; Kirkpatrick, Nathaniel D. ; Wharton, J. Taylor ; Wang, Jian ; Hatch, Kenneth D ; Auersperg, Nelly ; Utzinger, Urs ; Gershenson, David ; Bast, Robert ; Zou, Changping. / 4-HPR modulates gene expression in ovarian cells. In: International Journal of Cancer. 2006 ; Vol. 119, No. 5. pp. 1005-1013.
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