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

An immortal cell line was established by transfecting a myc oncogene into rat embryo cells (REC:myc). This cell line was diploid, contact inhibited and grew well in culture. Exposure to a single 200 cGy dose of 6 MeV alpha-particles transformed these cells with a frequency of focus formation of approximately 3.6 x 10(-4) compared with a transformation frequency of < 7.8 x 10(-6) for primary cultures of REC. Isolates of alpha-particle-induced REC:myc (REC:myc:alpha) foci displayed anchorage-independent growth in soft agar and were tumourigenic in nude mice. Molecular studies demonstrated no alteration of gene structure or expression of the transfected or of the endogenous c-myc genes. Similarly, there was no alteration of the structure of Ha-ras, Ki-ras, or N-ras. The expression of Ha-ras, Ki-ras, N-ras and raf was not altered significantly. Assay for dominant oncogenes via DNA-mediated gene transfer into NIH3T3 cells was positive for nine of 13 REC:myc:alpha transformants. All NIH3T3 isolates contained bands hybridizing to rat repetitive DNA. NIH3T3 transformants from a tertiary round of transfection were analysed by Southern blot analysis for the presence of Ki-ras, N-ras, raf, trk, abl, fms, src, mos, fos, sis, fps, erbA, erbB or neu oncogenes of REC origin, and none were detected. Tertiary NIH3T3 transformants from three REC:myc:alpha transformants contained bands corresponding to Ha-ras but no point mutations were identified at the known hotspots of exons 1 or 2 of the donor REC:myc:alpha transformants. The inactivation of the tumour suppressor genes Rb, and p53, and the anti-metastasis gene, nm23, was evaluated by Southern and Northern hybridization analysis. Southern blots demonstrated that at least one allele of Rb, p53 and nm23 was present and no large scale structural changes were detected. No expression of Rb or p53 was detected in REC:myc or the alpha-particle-induced REC:myc transformants. The expression of nm23 was not altered in the transformed cell lines. While the analysis of the role of tumour suppressor gene inactivation in radiation-induced cell transformation is only in the initial stages, the results of DNA-mediated gene transfer into NIH3T3 cells suggest that unidentified dominant oncogenes are associated with alpha-particle-induced transformation in vitro.
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PMID:Molecular analysis of rat embryo cell transformants induced by alpha-particles. 790 39

Following an earlier study linking monosomy 9 with recurrence of transitional cell carcinomas (TCCs) of the urinary bladder, 109 primary and recurrent TCCs (from 47 patients) were examined to explore genetic alterations at chromosome 9 associated with recurrence. Patient DNA was microdissected and extracted from archival tissue sections and analysed for loss of heterozygosity (LOH) at three regions on chromosome 9 where tumour suppressor genes (TSGs) are known to reside (INK 4A, DBC1, and TSC1). Patients were categorized into two groups, non-recurrent TCC (NR, n=18) and recurrent TCC (REC, n=29). It was noted that 12% of NR tumours, compared with 54% of REC primary tumours (p=0.01), had LOH at all informative markers spanning the TSC1 region. The risk of recurrence was significantly higher in patients with deleted TSC1 than in those who retained the TSC1 region (p=0.035). Levels of LOH at DBC1 or INK 4A were not significantly different in NR tumours than in REC primary tumours and recurrence-free survival was not affected by loss of either of these genes. Loss of all informative markers spanning chromosome 9 was observed in 0% of NR tumours compared with 25% of REC primary tumours (p=0.04). The probability of recurrence was also significantly increased in patients who had LOH at all informative markers spanning chromosome 9 (p=0.016), confirming earlier fluorescence in situ hybridization results. This study provides further evidence that recurrence in bladder cancer is a distinct event, with underlying molecular causes. It also identifies the TSC1 locus as a candidate for a TSG, which drives recurrence in a proportion of TCC patients. Loss of all informative markers, including those residing in the TSC1 region, spanning chromosome 9 was also linked to recurrence.
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PMID:Identification of loci associated with putative recurrence genes in transitional cell carcinoma of the urinary bladder. 1192 Jul 32

Inhibition of the tumour suppressor p53 by PFT (pifithrin-alpha) promotes p53-mediated apoptosis and protects against doxorubicin-induced apoptosis. The present study was carried out to evaluate the effect of PFT on the radioprotective potential of Podophyllum hexandrum fraction (REC-2006) in HepG2 (p53++) cell line. REC-2006 (10-5 microg/ml) treatment at 2 h before irradiation (10 Gy) rendered 80+/-3% protection in HepG2 cells, whereas PFT debilitated the radioprotective potential of REC-2006. REC-2006 increased the expression of Hsp70 (heat-shock protein 70), HSF1 (heat-shock factor 1) and Bcl-2 in irradiated HepG2 cells, whereas PFT when treated with REC-2006 decreased the expression of Hsp70, HSF1 and Bcl-2 in HepG2 cells. REC-2006 facilitated post-irradiation DNA repair by pausing cell-cycle progression at G1- and G2-phase, whereas no such cell-cycle arrest was observed in irradiated HepG2 cells pretreated with PFT in irradiated HepG2 cells. No change was observed in Mdm2 (murine double minute 2) and Ras-GAP (Ras-GTPase-activating protein) expression with or without PFT treatment. Decrease in the expression of caspase 3 and Bax was observed in HepG2 cells when REC-2006 treatment was given 2 h before irradiation; however, PFT treatment increased the expression of Bax leading to apoptosis. It can be concluded that p53 expression plays a major role in the REC-2006-mediated protection against acute irradiation in HepG2 cells. PFT treatment reduced the radioprotective efficacy of REC-2006 by inhibiting the expression of HSF1 and Hsp70 and thereby the expression of Bcl-2, by up-regulating the cell-cycle-regulatory proteins and therefore reducing the span of time for DNA repair and also by inducing Bax-mediated apoptosis. PFT did not, however, show any effect on p53 regulating protein (Mdm2) and pro-survival protein (Ras-GAP).
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PMID:Pifithrin-alpha decreases the radioprotective efficacy of a Podophyllum hexandrum Himalayan mayapple fraction REC-2006 in HepG2 cells. 1940 72