Gene 33 inhibits apoptosis of breast cancer cells and increases poly(ADP-ribose) polymerase expression.
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.
Xu
Jie
J
Department of Pathology, Division of Molecular and Cellular Pathology, University of Alabama, Birmingham, AL 35294-0019, USA.
Keeton
Adam B
AB
Wu
Liyu
L
Franklin
John L
JL
Cao
Xu
X
Messina
Joseph L
JL
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; C484017:ERRFI1 protein, human; D007328:Insulin; D025521:Tumor Suppressor Proteins; D014212:Tretinoin; D004815:Epidermal Growth Factor; D011065:Poly(ADP-ribose) Polymerases