PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 10463617

Expression level of Bcl-2 determines anti- or proapoptotic function.

N Shinoura·Y Yoshida·M Nishimura·Y Muramatsu·A Asai·T Kirino·H Hamada
View original source ↗Export metadata ↓

Abstract

Bcl-2 is an oncogene with antiapoptotic function. However, Bcl-2 is converted to a Bax-like death effector by caspases, suggesting that the expression of Bcl-2 may not favor the growth of cancers. We introduced the Bcl-2 gene to gliomas via adenovirus (Adv; Adv-Bcl-2) with the Adv for Fas (Adv-Fas) and the Adv for Fas ligand (Adv-FL) to evaluate the antiapoptotic function of Bcl-2. In U251 glioblastoma cells, Bcl-2 at a low level of expression repressed apoptosis induced by Adv-Fas and Adv-FL, whereas Bcl-2 at a high level of expression did not. On the other hand, Bcl-X(L) showed antiapoptotic function against Fas-mediated apoptosis, irrespective of its expression level. In glioblastoma cells, induction of Bcl-2 alone at a high level induced apoptosis, whereas induction of Bcl-X(L) alone did not. As the multiplicity of infection of Adv-Bcl-2 was increased, the quantity of a cleaved product of Bcl-2 increased. Induction of caspase-inhibitory genes (CrmA and p35) inhibited apoptosis induced by Adv-Bcl-2. Induction of Bcl-2 led to alteration of the membrane potential and structure of the mitochondria. In summary, although Bcl-2 at a low level of expression was antiapoptotic, Bcl-2 at a high level of expression was proapoptotic to Fas-mediated apoptosis. Overexpression of Bcl-X(L) was consistently antiapoptotic to Fas-mediated apoptosis.

Explore related subjects

ApoptosisFas Ligand ProteinGene Expression Regulation, NeoplasticGliomaHumansMembrane GlycoproteinsProto-Oncogene Proteins c-bcl-2Tumor Cells, Culturedfas ReceptorJournal ArticleResearch Support, Non-U.S. Gov't

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

N Shinoura, Y Yoshida, M Nishimura, Y Muramatsu, A Asai, T Kirino, H Hamada. 1999-08-15. Expression level of Bcl-2 determines anti- or proapoptotic function.. https://pubmed.ncbi.nlm.nih.gov/10463617/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2026

RUNX3: a regulator of macrophage apoptosis with positive prognostic impact in sepsis.

BACKGROUND: Sepsis, a life-threatening condition, remains a leading cause of mortality globally. Transcription factors (TFs) play a pivotal role in its pathogenesis. RUNX3, a member of the RUNX family, has been implicated in immune regulation, but its function in sepsis remains unclear. OBJECTIVE: To determine whether RUNX3 expression is altered in sepsis and associated with patient prognosis, and to investigate its function and potential transcriptional regulatory targets in macrophages. METHODS: We analyzed RNA-seq data from sepsis patients to identify differentially expressed TFs and examined the prognostic impact of RUNX3 by Kaplan-Meier survival analysis. RUNX3 was stably overexpressed in RAW264.7 macrophages, and cell proliferation and apoptosis were assessed by EdU and flow cytometry assays. RNA-seq of RUNX3-overexpressing cells was performed to identify potential transcriptional regulatory targets, a subset of which was validated by RT-qPCR. RESULTS: RUNX3 expression was downregulated in sepsis patients, and low RUNX3 expression was associated with poor prognosis. RUNX3 overexpression promoted proliferation and inhibited apoptosis in RAW264.7 cells. Integrating RNA-seq with public RUNX3 binding data identified 89 potential transcriptional regulatory targets, among which Tgfbr3, Tgfbi, Il2rb, Gbp2, Gzmb, and Ptgds were confirmed as RUNX3-responsive by RT-qPCR. High expression of these targets was associated with favorable prognosis in sepsis patients. CONCLUSION: RUNX3 is closely associated with the prognosis of sepsis, and its overexpression promotes proliferation and suppresses apoptosis in macrophages, potentially by regulating downstream target genes, providing a novel perspective on sepsis pathogenesis.

Apoptosis↗
PubMed2026

Identification and validation of an alternatively spliced novel isoform of maspin that modulate genes involved in inflammatory and apoptotic pathways.

Maspin regulates cellular adhesion, migration, apoptosis, angiogenesis, and tumor suppression in a tissue and context-dependent manner. Its functional diversity is governed largely thorough extracellular matrix interactions, subcellular localization, and the reactive center loop (RCL), although the structural details are not well understood. To examine whether alternative splicing contributes to this heterogeneity, we analysed the SERPINB5 gene using a computational genomics approach and identified a novel 80 bp coding exon upstream of the first coding exon (E1). The alternatively spliced transcript was validated in human skin and esophagus by semi-nested touchdown PCR, quantitative real-time PCR, and Sanger sequencing. Recombinant B5N displayed a red-shifted fluorescence emission spectrum, indicating a more solvent-exposed conformation, which was supported by molecular dynamics simulations showing greater exposure of the nuclear localization signal (NLS) and the reactive center loop. Enzyme kinetic assays demonstrated concentration-dependent enhancement of tissue plasminogen activator (tPA) activity by both isoforms. In HaCaT cells, wildtype maspin produced stronger antiproliferative and anti-migratory effects, whereas B5N was only mildly antiproliferative. Annexin V/7-AAD staining revealed that wildtype maspin induced higher early apoptosis and cell death, while B5N produced lower overall cell death but a greater proportion of late apoptotic cells. RNA-seq of transfected HaCaT cells identified differentially expressed genes enriched in inflammatory, antiviral, and apoptotic pathways, which was validated by qPCR, and several of these were markedly upregulated in SARS-CoV-2 infected A549 cells. Thus, a novel N-terminally extended maspin isoform with differentially regulated gene profile is identified and validated in this study.

Apoptosis↗
PubMed2026

Thyroxine enhances breast cancer cell survival and proliferation via TRβ1-Dependent PI3K/AKT signaling.

Thyroid hormones (TH) influence tumor biology through both genomic and non-genomic mechanisms. Specifically, thyroxine (T4) activates signaling pathways linked to cancer progression through interactions with nuclear receptors, such as TRβ1, and membrane receptors, including integrin αvβ3. Nevertheless, the precise role of T4 in breast cancer cell behavior and its underlying molecular mechanisms remain incompletely understood. The effects of physiological concentrations of T4 (10-9 M) on proliferation, cell viability, apoptotic signaling, and activation of intracellular pathways were evaluated in human mammary cell lines. Tumor cell lines (MCF-7 and MDA-MB-231) and the non-tumor mammary epithelial cell line MCF-10A were treated with T4 alone or in combination with the thyroid hormone receptor antagonist 1-850. Cell proliferation was measured using the MTT assay, and viability was determined by trypan blue exclusion. Protein expression and signaling pathways were analyzed by Western blot, including assessment of apoptotic markers (caspases, PARP, Bax, Bcl-2), PCNA, steroid hormone receptors, and signaling mediators such as PI3K, AKT, and ERK. Immunocytochemistry was used to evaluate TRβ1, integrin αvβ3, and Ki67 expression. T4 treatment increased proliferation and survival in hormone-sensitive tumor cells, accompanied by modulation of apoptosis-related proteins and activation of the PI3K/AKT pathway. The antagonist 1-850 selectively attenuated TRβ1-dependent effects, enabling distinction between genomic and integrin-mediated mechanisms. These effects were observed exclusively in hormone-sensitive tumor cells. These findings support a role for T4 in breast cancer progression and identify TH-related signaling pathways as potential therapeutic targets.

Apoptosis↗