Gene 33 inhibits apoptosis of breast cancer cells and increases poly(ADP-ribose) polymerase expression

Jie Xu, Adam B. Keeton, Liyu Wu, John L. Franklin, Xu Cao, Joseph L. Messina

Research output: Contribution to journalArticle

Abstract

The structure of the Gene 33 protein suggests that it plays a role in intracellular signaling and Gene 33 is induced by many mitogenic and stressful stimuli. Previously, we found that Gene 33 expression is significantly induced by retinoic acid (RA), insulin and synergistically by both in a liver-derived cell line. In the present study, we investigated the basal expression and regulation of Gene 33 in multiple human breast cancer cell lines. These cell lines expressed different levels of Gene 33 protein, but Gene 33 protein was not regulated by RA or insulin, either alone, or in combination. However, epidermal growth factor (EGF) induced Gene 33 expression in SK-BR-3 cells and this induction was inhibited by co-treatment with RA. There was a strong correlation between endogenous basal Gene 33 expression and doubling time. Exogenous expression of Gene 33 in MCF-7 cells did not affect cell cycle distribution, but inhibited apoptosis and specifically increased the level of Poly(ADP-ribose) Polymerase (PARP-1) protein. This suggests that Gene 33 promotes breast cancer cell growth by an anti-apoptotic rather than a mitogenic effect, possibly involving up-regulation of PARP-1.

Original languageEnglish (US)
Pages (from-to)207-215
Number of pages9
JournalBreast Cancer Research and Treatment
Volume91
Issue number3
DOIs
StatePublished - Jun 2005
Externally publishedYes

Fingerprint

Poly(ADP-ribose) Polymerases
Tretinoin
Apoptosis
Breast Neoplasms
Gene Expression
Cell Line
Genes
Insulin
Proteins
MCF-7 Cells
Gene Expression Regulation
Epidermal Growth Factor
Cell Cycle
Up-Regulation
Liver
Growth
Poly (ADP-Ribose) Polymerase-1

Keywords

  • Apoptosis
  • Breast cancer
  • Gene 33
  • Poly(ADP-ribose) polymerase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Gene 33 inhibits apoptosis of breast cancer cells and increases poly(ADP-ribose) polymerase expression. / Xu, Jie; Keeton, Adam B.; Wu, Liyu; Franklin, John L.; Cao, Xu; Messina, Joseph L.

In: Breast Cancer Research and Treatment, Vol. 91, No. 3, 06.2005, p. 207-215.

Research output: Contribution to journalArticle

Xu, Jie ; Keeton, Adam B. ; Wu, Liyu ; Franklin, John L. ; Cao, Xu ; Messina, Joseph L. / Gene 33 inhibits apoptosis of breast cancer cells and increases poly(ADP-ribose) polymerase expression. In: Breast Cancer Research and Treatment. 2005 ; Vol. 91, No. 3. pp. 207-215.
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AB - The structure of the Gene 33 protein suggests that it plays a role in intracellular signaling and Gene 33 is induced by many mitogenic and stressful stimuli. Previously, we found that Gene 33 expression is significantly induced by retinoic acid (RA), insulin and synergistically by both in a liver-derived cell line. In the present study, we investigated the basal expression and regulation of Gene 33 in multiple human breast cancer cell lines. These cell lines expressed different levels of Gene 33 protein, but Gene 33 protein was not regulated by RA or insulin, either alone, or in combination. However, epidermal growth factor (EGF) induced Gene 33 expression in SK-BR-3 cells and this induction was inhibited by co-treatment with RA. There was a strong correlation between endogenous basal Gene 33 expression and doubling time. Exogenous expression of Gene 33 in MCF-7 cells did not affect cell cycle distribution, but inhibited apoptosis and specifically increased the level of Poly(ADP-ribose) Polymerase (PARP-1) protein. This suggests that Gene 33 promotes breast cancer cell growth by an anti-apoptotic rather than a mitogenic effect, possibly involving up-regulation of PARP-1.

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