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. 2009 Jun 1;1(3):112-118.
doi: 10.4255/mcpharmacol.09.14.

PUMA Kills Stem Cells to Stall Cancer?

Jian Yu  1
Affiliations

PUMA Kills Stem Cells to Stall Cancer?

Jian Yu. Mol Cell Pharmacol. .

Abstract

Apoptosis evasion is a hallmark of human cancer. PUMA is a BH3-only Bcl-2 family protein that mediates both p53-dependent and independent apoptosis. However, its role in tumor suppression had not been well established. Our recent work provides direct evidence that PUMA plays an important role in suppressing intestinal tumorigenesis in two mouse models including (i) the azoxymethane (AOM)/dextran sulfate sodium salt (DSS)-treated mice and (ii) APC(Min/+) mice. The activities of PUMA appeared to be in the intestinal stem cells, and involve both p53-dependent response to DNA damage, and p53-independent mechanisms triggered by inflammation. Our data suggest that the interplay between different apoptotic pathways in intestinal stem cells underlie the initiation of intestinal carcinogenesis, and should be considered in the context of cancer prevention and therapy.

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Conflict of interest statement

Conflicts of Interest

No potential conflicts of interest to disclose.

Figures

Figure 1
Figure 1. p53-dependent PUMA induction contributes to AOM-induced apoptosis but not proliferation
(A)The parental or p53 KO HCT116 cells were treated with 20 ng/ml AOM for the indicated time. The levels of PUMA, p53 and tubulin were analyzed by Western blotting. (B) The proliferation of the colonic crypts was determined by BrdU immunohistochemistry (IHC) in WT, PUMA KO and p53 KO mice 72 hr following AOM injection. (C) Active caspase-3 (brown, arrow head) in the colonic crypts 8 hr after AOM injection was detected by IHC.
Figure 2
Figure 2. PUMA expression is induced by DSS in the colon
WT mice were subjected to DSS treatment in drinking water for the indicated time, D (day). The levels of PUMA, p53 and tubulin in the intestinal mucosa were analyzed by Western blotting.
Figure 3
Figure 3. A model of PUMA-mediated tumor suppression
PUMA is activated by transcription factors in response to stress, leading to apoptosis induction and tumor suppression. DNA damage or activated oncogenes induces PUMA through p53 to promote apoptosis. Inflammatory cytokines induces PUMA through NFκB to promote apoptosis. DNA damage, inflammatory cytokines and perhaps yet-to-be identified mediators and transcription factors (TF) might provoke PUMA-dependent apoptosis during inflammation.
See this image and copyright information in PMC

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