OVCA2 is downregulated and degraded during retinoid-induced apoptosis

Amanda H. Prowse, Lisa Vanderveer, Simon W F Milling, Zhong Zong Pan, Roland L. Dunbrack, Xiangxi Xu, Andrew K. Godwin

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Retinoids, the natural and synthetic derivatives of vitamin A, have been shown to regulate the growth and differentiation of a wide variety of cell types and consequently have enormous potential as chemotherapeutic agents. We have previously identified 2 genes, termed OVCAI and OVCA2, which are located in a small region showing a high frequency of allelic loss in breast and ovarian tumors and share a common exon. Recent studies have suggested that expression of OVCAI may be influenced by retinoids. Therefore, we analyzed the expression of OVCAI and OVCA2 in cells in response to treatment with all-trans retinoic acid (RA) and N.(4-hydroxyphenyl)retinamide (4HPR), or under conditions of low serum and confluence, to determine further the roles of OVCAI and OVCA2 in cell growth, apoptosis and differentiation. We show that OVCA2 mRNA and protein are ubiquitously expressed and that they are downregulated in the lung cancer cell line Calu-6 after treatment with RA and 4HPR. In addition, we observed that OVCA2 protein is proteolytically degraded in response to RA and 4HPR treatment in a time- and dose-dependent manner in the promyelocytic leukemia cell line HL60. In contrast, expression of the candidate tumor suppressor OVCAI was not downregulated by these treatments. Furthermore, we demonstrate that OVCA2 is evolutionarily conserved and shows regional homology with dihydrofolate reductases (DHFRs), specifically with hydrolase folds found in α-β hydrolases. Our results are in contrast to a previous report and show that OVCA2, not OVCAI mRNA and protein, is downregulated in response to RA and 4HPR.

Original languageEnglish
Pages (from-to)185-192
Number of pages8
JournalInternational Journal of Cancer
Volume99
Issue number2
DOIs
StatePublished - May 10 2002
Externally publishedYes

Fingerprint

Retinoids
Tretinoin
Down-Regulation
Apoptosis
Hydrolases
Fenretinide
Cell Line
Messenger RNA
Tetrahydrofolate Dehydrogenase
Proteins
Loss of Heterozygosity
Growth
Vitamin A
Exons
Lung Neoplasms
Leukemia
Breast Neoplasms
Serum
Genes
retinamide

Keywords

  • 4HPR
  • All-trans retinoic acid
  • N-(4-hydroxyphenyl)retinamide
  • OVCA1
  • OVCA2
  • RA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Prowse, A. H., Vanderveer, L., Milling, S. W. F., Pan, Z. Z., Dunbrack, R. L., Xu, X., & Godwin, A. K. (2002). OVCA2 is downregulated and degraded during retinoid-induced apoptosis. International Journal of Cancer, 99(2), 185-192. https://doi.org/10.1002/ijc.10334

OVCA2 is downregulated and degraded during retinoid-induced apoptosis. / Prowse, Amanda H.; Vanderveer, Lisa; Milling, Simon W F; Pan, Zhong Zong; Dunbrack, Roland L.; Xu, Xiangxi; Godwin, Andrew K.

In: International Journal of Cancer, Vol. 99, No. 2, 10.05.2002, p. 185-192.

Research output: Contribution to journalArticle

Prowse, AH, Vanderveer, L, Milling, SWF, Pan, ZZ, Dunbrack, RL, Xu, X & Godwin, AK 2002, 'OVCA2 is downregulated and degraded during retinoid-induced apoptosis', International Journal of Cancer, vol. 99, no. 2, pp. 185-192. https://doi.org/10.1002/ijc.10334
Prowse AH, Vanderveer L, Milling SWF, Pan ZZ, Dunbrack RL, Xu X et al. OVCA2 is downregulated and degraded during retinoid-induced apoptosis. International Journal of Cancer. 2002 May 10;99(2):185-192. https://doi.org/10.1002/ijc.10334
Prowse, Amanda H. ; Vanderveer, Lisa ; Milling, Simon W F ; Pan, Zhong Zong ; Dunbrack, Roland L. ; Xu, Xiangxi ; Godwin, Andrew K. / OVCA2 is downregulated and degraded during retinoid-induced apoptosis. In: International Journal of Cancer. 2002 ; Vol. 99, No. 2. pp. 185-192.
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