Disease relevance of BCL2L1

• Stable transfection of U2-OS cells with bcl-xL cDNA conferred a low level of drug resistance to cisplatin, suggesting that overexpression of this gene contributes to the cisplatin-resistant phenotype of this osteosarcoma cell system [1].
• The bcl-xL gene level correlated with the number of apoptotic lymphoma cells labeled by terminal deoxytransferase-catalyzed DNA nick-end labeling (TUNEL) assays (r = -0.7736) [2].
• The value of bcl-xL gene expression as a prognostic marker in follicular lymphoma should thus be considered [2].
• Compared with 10 patients with reactive follicular hyperplasia, the bcl-xL gene was overexpressed in patients with follicular lymphoma at a higher level in microdissected lymphoma cells [2].
• Furthermore, the expression of bcl-2 mRNA was significantly enhanced in cutaneous lesions of adult and pediatric patients, while bcl-xL mRNA levels were only slightly increased in pediatric, but not in adult patients with mastocytosis [3].

High impact information on BCL2L1

• When stably transfected into an IL-3-dependent cell line, bcl-xL inhibits cell death upon growth factor withdrawal at least as well as bcl-2 [4].
• In vivo, bcl-xS mRNA is expressed at high levels in cells that undergo a high rate of turnover, such as developing lymphocytes [4].
• Downregulation of intimal cell bcl-xL expression with the use of antisense oligonucleotides induced apoptosis and acute regression of vascular lesions [5].
• These findings indicate that apoptosis regulatory genes such as bcl-xL are critical determinants of intimal lesion formation and that targeted apoptosis may be a novel therapy for intimal vascular disease [5].
• In the classic genetic model Caenorhabditis elegans, the pro-apoptotic protein CED-4 activates the CED-3 caspase and is inhibited by the Bcl-2-like protein CED-9 [6].

Chemical compound and disease context of BCL2L1

• EXPERIMENTAL DESIGN: Antisense bcl-2/bcl-xL (4625), antisense PKAI (AS-PKAI), and ZD1839 ("Iressa"), a selective EGFR tyrosine kinase inhibitor, were administered as single agents and in combination against GEO colon and ZR-75-1 breast cancer cell lines in vitro and to mice bearing s.c. GEO human tumor xenografts in vivo [7].
• Taxol and estramustine-induced modulation of human prostate cancer cell apoptosis via alteration in bcl-xL and bak expression [8].

Biological context of BCL2L1

• Since the nuclear-to-cytoplasm events preceding the release of cytochrome C were similar in all cell lines, and increased expression of either the SOD2 or the BCL2L1 transgene provided radiation protection, we conclude that events at the level of the mitochondria are critically involved in radiation-induced apoptosis [9].
• In T cells activated in vitro, up-regulation of bcl-xL, has previously been correlated with general apoptosis resistance [10].
• One is the expression of nonfunctional receptors, decoy receptors, and molecules that block cell death, such as bcl2 and bcl-xL [11].
• Levels of BCL2 were high during early gestation, followed by significantly elevated levels of BCL2L1 at midgestation [12].
• Exposure to 5-azaC altered the expression of genes involved in imprinting (IGF2) or pro-apoptosis (BAX), whereas there was a reduction in the expression of the main enzyme responsible for replicating the DNA methylation pattern (DNMT1) and anti-apoptosis (BCL2L1) [13].

Anatomical context of BCL2L1

• Bcl-X was strongly increased during the terminal differentiation stages of human and mouse erythroblasts, reaching maximum transcript and protein levels at the time of maximum hemoglobin synthesis [14].
• This is accompanied by lowered bcl2-like immunoreactivity and increased poly(ADP-ribose) polymerase cleavage and cytochrome c translocation into the cytosol [15].
• To assess its clinical significance in patients with follicular lymphoma, realtime quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis of bcl-xL gene expression was investigated in whole lymph node sections and laser-microdissected lymphoma cells of 27 patients [2].
• In patients with mastocytosis, the expression of bcl-2 protein but not bcl-xL in cutaneous mast cells was significantly enhanced, compared to healthy controls [3].
• In contrast to the skin lesions, bone marrow infiltrates of patients with systemic mastocytosis showed only low or absent immunoreactivity for bcl-2, but marked expression of bcl-xL [3].

Associations of BCL2L1 with chemical compounds

• Clinically, a high bcl-xL level was significantly associated with multiple sites of extranodal involvement (P =.0020), elevated lactate dehydrogenase level (P =.0478), and an International Prognostic Index indicating high risk (P =.0235) [2].
• Rapamycin-resistant proliferation of CD8+ T cells correlates with p27kip1 down-regulation and bcl-xL induction, and is prevented by an inhibitor of phosphoinositide 3-kinase activity [16].
• When activated, these death ligands engage pro-survival Bcl-2-like proteins via the BH3 domain, inactivating their function [17].
• STI571 failed to activate caspase cascades or to suppress expression of survival genes (bcl-xL) in resistant cells [18].
• By GenBank database searches and PCR, we have identified a novel human Bcl2-like gene, Bcl2-L-10, which contains conserved BH4, BH1 and BH2 domains but lacks BH3 domain [19].

Regulatory relationships of BCL2L1

• Treatment with a subtoxic concentration of a bispecific bcl-2/bcl xL antisense oligonucleotide cooperated with okadaic acid to down-regulate bcl-2 and sensitize cyclin D1-overexpressing cells to okadaic acid [20].
• Effect of bax, bcl-2 and bcl-xL on regulating apoptosis in tissues of normal liver and hepatocellular carcinoma [21].
• Accordingly, we found that SCF up-regulates Bcl-2 and Bcl-X L in erythroid precursors and that exogenous expression of these proteins protects erythroblasts from caspase activation and death induced by chemotherapeutic agents [22].
• The ability of CD28 to enhance survival during T cell activation correlated positively with its ability to up-regulate the protein product of the cell survival gene bcl-xL [23].
• In contrast to many other anticancer agents to which the apoptotic response is decreased because of p53 mutations, our data suggest that the bcl-2/bcl-xL bispecific antisense oligonucleotide 4625 effectively induces p53-independent apoptosis in human C8161 melanoma cells [24].

Other interactions of BCL2L1

• In addition to murine (m) bcl-xL and mbcl-xS, we have cloned a novel cDNA isoform that we designate mbcl-x delta TM [25].
• Using in vitro protein-protein interaction assays, all BNIP1 variants were shown to interact with BCL2 and also with BCL2L1 (previously Bcl-xL) [26].
• Similar BAX and BCLX protein expression was observed in LGG and HGG [27].
• However, BCL-Xs and BAK were weakly expressed in K562, as were Bcl-X, BAD and BAK in the VAL line [28].
• Inducing apoptosis of human nasopharyngeal carcinoma cell line CNE-2Z by bcl-xL short hairpin RNA [29].

Analytical, diagnostic and therapeutic context of BCL2L1

• The expression levels of antiapoptotic regulatory proteins (BCL2 and BCL2L1) and enzymes involved in apoptosis (caspases 3, 6, 7, 9, and 10) were assessed by immunoblotting throughout gestation and postpartum [12].
• To investigate whether an altered regulation of mast cell apoptosis might be involved in the pathogenesis of mastocytosis, expression of the apoptosis-preventing molecules bcl-2 and bcl-xL was studied by immunohistochemistry in skin and bone marrow lesions of mastocytosis patients [3].
• METHODS: The expression of bax, bcl-2 and bcl-xL mRNA of normal liver and HCC was measured by Northern blot [21].
• Southern blot for TPX2 and BCL2L1 identified the former as the gene with the highest level of amplification for these two proposed candidate genes of importance [30].
• METHODS: DNA extraction, PCR amplification, and direct sequencing of the VSX1, BCL2L1, and ID1 genes were performed in 14 affected patients (12 families) as well as in unaffected family members and healthy control subjects [31].

References