Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A detailed deletion mapping of a series of human prostatic carcinomas, using restriction fragment length polymorphism (RFLP) analysis of all chromosomes, showed allelic losses on individual chromosomes at variable frequencies. Allelic losses occurred on chromosomal arms 8p, 10pq, 16q and 18q in more than 30% of the cases. Losses of genetic information from one or two of the chromosomes 8, 10, or 16 were always present in tumors showing allelic losses, indicating that genes on these chromosomes have a central role in prostatic cancer. A more extensive study of these chromosomes was thus carried out and showed the highest frequency of allelic deletions to occur on the short arm of chromosome 8 (65%) (where the minimally deleted region was between the PLAT locus and pter). The long arm of chromosome 16 had allelic deletions in 56% of informative cases, with three different break points (the most distal being between D16S4 and D16S7). Chromosome 10 exhibited a complex deletion pattern, showing allelic losses from both the short (p) and the long (q) arms, evidence of non-reciprocal translocations of the q arm, and monosomy in some cases. Our data indicate that tumor suppressor genes involved in the oncogenesis of prostatic carcinoma may be localized between 8pter and the PLAT locus and that additional/alternative tumor suppressor gamma are likely to be localized on chromosome 10 and on the long arm of chromosome 16. More aggressive tumors were accompanied by a high or frequency of allelic losses.
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PMID:Recessive genetic mechanisms in the oncogenesis of prostatic carcinoma. 168 23

In two androgen-dependent (FGC and P70) and two androgen-independent (LNO and R) sublines of the prostate cancer model LNCaP numerical and structural aberrations of chromosome 8 were investigated in detail. The techniques used were whole chromosome paint (WCP) and fluorescence in situ hybridization (FISH) with three cosmid probes mapping to different parts of the p-arm (D8S7 (8p23.3), LPL (8p22) and PLAT (8p11.1)). By WCP all four cell lines showed four copies of chromosome 8 in most cells. However, FISH demonstrated that in all sublines deletions in the 8p region were present. The majority of both FGC and P70 had two copies of cosmids D8S7 and LPL. The cosmid PLAT showed a broader distribution (1-4 copies), especially in P70. Compared with FGC and P70, both LNO and R showed a larger number of copies (3 or 4) of all three cosmid loci. It is discussed that this difference is probably the result of nondisjunction as a reaction to loss of other sequences on 8p, possibly the tumor suppressor gene (TSG) mapping to 8p21. The fact that both sublines LNO and R are androgen-independent raises the possibility of a link between TSG loss on 8p and androgen independence.
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PMID:Characterization of chromosome 8 aberrations in the prostate cancer cell line LNCaP-FGC and sublines. 1009 47

15-Lipoxygenase-2 protein has been reported to play an important role in normal development of prostate, lung, skin, and cornea tissues. It behaves as a suppressor of prostate cancer development by restricting cell cycle progression and implicating a possible protective role against tumor formation. On the basis of the above report, we selected 15-LOX-2 protein to study the structural classification and functional relationship with associated protein network at computational level. Sequence alignment and protein functional study shows that it contains a highly conserved LOX motif. PLAT domain with PF01477 and LH2 domain with PF00305 were successfully observed. Arachidonate 5-lipoxygenase (PDB ID: 3O8Y) was selected as a template with 42% identity. 3D structure was successfully predicted and verified. Qualitative analysis suggests that the predicted model was reliable and stable with best quality. Quantitative study shows that the model contained expected volume and area with best resolution. Predicted and best evaluated model has been successfully deposited to PMDB database with PMDB ID PM0078035. Active site identification revealed GLU(369), ALA(370), LEU(371), THR(372), HIS(373), LEU(374), HIS(376), SER(377), HIS(378), THR(385), LEU(389), HIS(394), PHE(399), LYS(400), LEU(401), ILE(403) and PRO(404) residues may play a major role during protein-protein, protein-drug and protein-cofactor interactions. STRING database result indicated that IL (4), GPX (2 and 4), PPARG, PTGS (1 and 2), CYP (2J2, 2C8, 4A11 and 2B6), PLA (2G2A, 2G4A, 2G1B and 2G6) and A LOX (5, 15, 12 and 12B) members from their respective gene families have network based functional association with 15-LOX-2.
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PMID:Qualitative and Quantitative analysis of 3D predicted arachidonate 15-lipoxygenase-B (15-LOX-2) from Homo sapiens. 2282 30

Prostate cancer (PCa) cells display abnormal expression of cytoskeletal proteins resulting in an augmented capacity to resist chemotherapy and colonize distant organs. We have previously shown that heme oxygenase 1 (HO-1) is implicated in cell morphology regulation in PCa. Here, through a multi 'omics' approach we define the HO-1 interactome in PCa, identifying HO-1 molecular partners associated with the integrity of the cellular cytoskeleton. The bioinformatics screening for these cytoskeletal-related partners reveal that they are highly misregulated in prostate adenocarcinoma compared with normal prostate tissue. Under HO-1 induction, PCa cells present reduced frequency in migration events, trajectory and cell velocity and, a significant higher proportion of filopodia-like protrusions favoring zippering among neighboring cells. Moreover forced expression of HO-1 was also capable of altering cell protrusions in transwell co-culture systems of PCa cells with MC3T3 cells (pre-osteoblastic cell line). Accordingly, these effects were reversed under siHO. Transcriptomics profiling evidenced significant modulation of key markers related to cell adhesion and cell-cell communication under HO-1 induction. The integration from our omics-based research provides a four molecular pathway foundation (ANXA2/HMGA1/POU3F1; NFRSF13/GSN; TMOD3/RAI14/VWF; and PLAT/PLAU) behind HO-1 regulation of tumor cytoskeletal cell compartments. The complementary proteomics and transcriptomics approaches presented here promise to move us closer to unravel the molecular framework underpinning HO-1 involvement in the modulation of cytoskeleton pathways, pushing toward a less aggressive phenotype in PCa.
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PMID:Heme oxygenase-1 in the forefront of a multi-molecular network that governs cell-cell contacts and filopodia-induced zippering in prostate cancer. 2803 57