当前位置： SCI文献检索 > EXPERIMENTAL AND MOLECULAR PATHOLOGY期刊下所有文献 > An Oct-1-based, feed-forward mechanism of apoptosis inhibited by co-culture with Raji B-cells: towards a model of the cancer cell/B-cell microenvironment.

An Oct-1-based, feed-forward mechanism of apoptosis inhibited by co-culture with Raji B-cells: towards a model of the cancer cell/B-cell microenvironment.

Abstract：

:A continuing conundrum of cancer biology is the dichotomous function of transcription factors that regulate both proliferation and apoptosis, seemingly opposite results. Previous results have indicated that regulated entry into the S-phase of the cell cycle can be anti-apoptotic. Indeed, tumor suppressor genes can be amplified in tumors and certain, slow growing cancers can represent a relatively poor prognosis, both phenomena likely related to reduced cancer cell apoptosis, in turn due to reduced, unproductive entry into S-phase. In this report, we demonstrate that the Oct-1 transcription factor, commonly considered pro-proliferative, indeed facilitates IFN-γ induced apoptosis in 5637 bladder carcinoma cells, consistent with the role of the retinoblastoma protein in down-regulating Oct-1 DNA binding activity and in suppressing IFN-γ induced apoptosis. More importantly, despite the commonly appreciated process of IFN-γ induced apoptosis, IFN-γ at low concentrations stimulated bladder cancer cell proliferation, consistent with apoptosis being dependent on an overstimulation of what is otherwise a pro-proliferative pathway. This observation is in turn consistent with a feed forward mechanism of apoptosis, whereby transcription factors activate proliferation-effector genes at relatively low levels, then apoptosis-effector genes when the transcription factors over-accumulate. Finally, Oct-1 mediated apoptosis is inhibited by co-culture with Raji B-cells, raising the question of whether the normal lymph node environment, or other microenvironments with high concentrations of B-cells, is protective against Oct-1 facilitated apoptosis?

journal_name

Exp Mol Pathol

journal_title

Experimental and molecular pathology

authors

Szekeres K,Koul R,Mauro J,Lloyd M,Johnson J,Blanck G

doi

10.1016/j.yexmp.2014.09.010

subject

Has Abstract

pub_date

2014-12-01 00:00:00

pages

585-9

issue

3

eissn

0014-4800

issn

1096-0945

pii

S0014-4800(14)00151-8

journal_volume

97

pub_type

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