Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The MCF-7 human breast carcinoma cell line is widely used as a model system by breast cancer researchers and cell biologists investigating apoptosis. Since its establishment 30 years ago, from a patient with metastatic breast cancer, the original MCF-7 cell population has undergone genetic drift to such an extent that numerous genetically diverse sublines now exist. For instance, it has been reported that MCF-7 cells have lost the region 3p21.3, to which the apoptosis regulatory protein and putative tumour suppressor LUCA-15 (also called RBM5 and H37) maps; however, LUCA-15 has been cloned from MCF-7 cells, and LUCA-15 expression analyses have been conducted using MCF-7 cells. To address this discrepancy, we characterized three MCF-7 sublines by Western blot, RT-PCR and finally genomic PCR analysis, and determined that one of the three had lost the LUCA-15 gene. Interestingly, loss of LUCA-15 was positively correlated with decreased susceptibility to the death-inducing ligand TNF-alpha. Subsequent overexpression of exogenous LUCA-15 was shown to enhance TNF-alpha-mediated apoptosis, suggesting that LUCA-15 may play a role in regulating the susceptibility of breast cancer cells to drug-induced apoptosis. These results not only reinforce the necessity of MCF-7 subline characterization, but provide the first evidence of an apoptotic modulatory role for LUCA-15 in a non-T cell line.
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PMID:Genetic instability of RBM5/LUCA-15/H37 in MCF-7 breast carcinoma sublines may affect susceptibility to apoptosis. 1533 70

Allele loss and genetic alteration in chromosome 3p, particularly in 3p21.3 region, are the most frequent and the earliest genomic abnormalities found in lung cancer. Multiple 3p21.3 genes exhibit various degrees of tumour suppression activity suggesting that 3p21.3 genes may function as an integrated tumour suppressor region through their diverse biological activities. We have previously demonstrated growth inhibitory effects and tumour suppression mechanism of the H37/RBM5 gene which is one of the 19 genes residing in the 370kb minimal overlap region at 3p21.3. In the current study, in an attempt to find, if any, mutations in the H37 coding region in lung cancer cells, we compared nucleotide sequences of the entire H37 gene in tumour versus adjacent normal tissues from 17 non-small cell lung cancer (NSCLC) patients. No mutations were detected; instead, we found the two silent single nucleotide polymorphisms (SNPs), C1138T and C2185T, within the coding region of the H37 gene. In addition, we found that specific allele types at these SNP positions are correlated with different histological subtypes of NSCLC; tumours containing heterozygous alleles (C+T) at these SNP positions are more likely to be associated with adenocarcinoma (AC), whereas, homozygous alleles (either C or T) are associated with squamous cell carcinoma (SCC) (p=0.0098). We postulate that, these two silent polymorphisms may be in linkage disequilibrium (LD) with a disease causative allele in the 3p21.3 tumour suppressor region which is packed with a large number of important genes affecting lung cancer development. In addition, because of prevalent loss of heterozygosity (LOH) detected at 3p21.3 which precedes lung cancer initiation, these SNPs may be developed into a marker screening for the high risk individuals.
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PMID:The two single nucleotide polymorphisms in the H37/RBM5 tumour suppressor gene at 3p21.3 correlated with different subtypes of non-small cell lung cancers. 1760 9

Previous work from our lab identified a 326 base-pair (bp) cDNA, termed Je2, which mapped to the antisense strand of intron 6 of the putative tumour suppressor gene RBM5/LUCA-15/H37, and functioned as an apoptosis suppressor. The purpose of the work described herein was to determine if Je2 is part of a larger transcript, to clone that transcript and to examine its ability to modulate RBM5 expression. Northern blot analyses in conjunction with strand-specific reverse transcription and PCR revealed two novel transcripts, one antisense and one sense, that included Je2 as well as RBM5 intron 4 sequence. Using rapid amplification of cDNA ends (RACE), a novel 1.4 kb product including Je2 and intron 4 was cloned. In vitro transcription/translation did not result in the production of any protein product, from either strand. Genomic DNA analysis revealed the presence of a putative promoter region 5' to Je2, suggesting that the cloned 1.4 kb RACE product represents an antisense transcript that initiates within intron 6 and terminates within intron 4 of the RBM5 gene. This novel antisense, non-coding RNA was termed LUST, for LUCA-15-specific transcript. Ectopic overexpression of LUST coincided with elevated expression of the full-length RBM5+5+6 alternative RBM5 RNA splice variant, and reduced expression of the truncated, cytotoxic RBM5+5+6t/Clone 26 alternative RBM5 RNA splice variant. A model is proposed whereby LUST functions co-transcriptionally to mask a sense-strand regulatory sequence, common to both RBM5+5+6 and RBM5+5+6t/Clone 26 transcripts, that when unmasked results in premature termination of RBM5+5+6, thereby generating the cytotoxic truncated product, RBM5+5+6t/Clone 26. These results suggest that LUST is a novel, functional, non-coding RNA that plays a role in determining the apoptotic fate of a cell by regulating the expression of RBM5 splice variants.
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PMID:Identification and characterisation of a novel antisense non-coding RNA from the RBM5 gene locus. 1955 72