当前位置： SCI文献检索 > Cancer Cell International期刊下所有文献 > Differential effects of HIF-α isoforms on apoptosis in renal carcinoma cell lines.

Differential effects of HIF-α isoforms on apoptosis in renal carcinoma cell lines.

Abstract：

BACKGROUND:Germline mutations in the von Hippel-Lindau (VHL) tumor suppressor gene predispose individuals to clear cell renal carcinomas, hemangioblastomas, and pheochromocytomas. The VHL gene product forms an ubiquitin E3 ligase complex, with regulation of hypoxia-inducible factor alpha (HIF-α) as its best known function. Lack of VHL expression has been shown previously to sensitize renal cells to apoptosis caused by certain cellular stresses. In this report, the role of HIF-α in apoptosis was investigated using two parent VHL-null renal carcinoma cell lines. METHODS:786-O and RCC10 renal carcinoma cell lines with manipulated levels of VHL, HIF-1α, or HIF-2α were subjected to cellular stresses and analyzed by western blotting for the abundance of apoptotic markers. RESULTS:Cell lines expressing mutant VHL proteins that were unable to regulate HIF-α had increased levels of apoptosis when irradiated with ultraviolet (UV) light. The influences of the two major isoforms of HIF-α, HIF-1α and HIF-2α, on apoptosis, were compared by creating cell lines in which levels of each isoform were modulated via short hairpin RNA interference. In UV-irradiated cells, HIF-2α expression was determined to promote apoptosis, whereas HIF-1α was anti-apoptotic. In cells deprived of either glucose or serum, HIF-1α expression was generally anti-apoptotic, while HIF-2α expression was observed to either promote apoptosis or have less of an influence on apoptosis, depending on the cell line used. CONCLUSIONS:HIF-1α and HIF-2α exerted distinct effects in each of the conditions tested, with expression of HIF-1α largely blocking apoptosis and HIF-2α generally promoting apoptosis. These results reinforce that HIF-1α and HIF-2α have distinct biological roles and that their relative expression levels may influence some therapeutic interventions that are dependent on apoptosis.

journal_name

Cancer Cell Int

journal_title

Cancer cell international

authors

Doonachar A,Gallo MD,Doukas D,Pasricha R,Lantsberg I,Schoenfeld AR

doi

10.1186/s12935-015-0175-3

subject

Has Abstract

pub_date

2015-02-22 00:00:00

pages

issn

1475-2867

pii

175

journal_volume

pub_type

杂志文章

在线工具

Differential effects of HIF-α isoforms on apoptosis in renal carcinoma cell lines.