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

作者：Szekeres Karoly; Koul Rudra; Mauro James; Lloyd Mark; Johnson Joseph; Blanck George^*

来源：Experimental and Molecular Pathology, 2014, 97(3): 585-589.

DOI：10.1016/j.yexmp.2014.09.010

• Feed-forward apoptosis
• Transcription factors
• Oct-1
• Interferon-gamma
• Bladder carcinoma
• B-cell microenvironment

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-gamma 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-gamma induced apoptosis. More importantly, despite the commonly appreciated process of IFN-gamma induced apoptosis, IFN-gamma 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 w

• 出版日期2014-12