Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclins and cyclin-dependent kinases (Cdks) are central to regulation of the cell cycle. Their abnormal expression may cause loss of cell-cycle control and result in autonomous cell growth, a critical feature of neoplasias. In this study, using immunoblotting, we analyzed the protein levels of several G1/S cyclins (cyclins D1, D2, D3, A, and E) and their respective Cdks (Cdk 2, 4, and 6) in 17 mouse squamous cell carcinomas (SCCs) and 18 mouse skin tumor cell lines. Overexpression of these cell cycle-related genes was frequent in tumors and cell lines. Of special interest was the fact that a group of cell lines that became more aggressive after animal passaging expressed more cyclins D2 and D3 than their respective parental lines did. In addition, SCCs had higher cyclin D3 expression levels than papillomas, and metastases had higher levels than the respective primary tumors, indicating that overexpression of cyclin D3 may be associated with increased aggressiveness of mouse SCC. Interestingly, overexpression of cyclin E was seen in most SCCs induced by a complete carcinogenesis protocol with benzo[a]pyrene (B(a)P) and only in a few SCCs induced by a two-stage carcinogenesis protocol using 7,12-dimethylbenz[a]anthracene as initiator. In contrast, more of the latter tumors overexpressed cyclin D1 and D2 than those induced by B(a)P. Thus, it is possible that different components of the cell-cycle machinery are involved in proliferative dysfunctions that take place during tumor development with different carcinogenesis protocols. Taken together, these results indicate that overexpression of G1 cyclins and their related Cdks is a significant molecular abnormality that could be involved in the process of tumor progression.
Mol Carcinog 1997 Mar
PMID:Increased expression of G1 cyclins and cyclin-dependent kinases during tumor progression of chemically induced mouse skin neoplasms. 911 84

In Central Europe seven lps species are characterized by differences in morphology, structure of galleries, host specificity and aggressiveness. These species were analysed by allozyme markers and by sequencing 567 bp of the mitochondrial cytochrome oxidase I gene, in order to define their phylogenetic relationships. Orthotomicus erosus and Tomicus minor were taken as outgroup species. The data revealed high inter-specific and low intra-specific sequence divergence. Plotting the observed sequence divergence caused by transversions (Tv) and transitions (Ts) and the level of saturation for Ts and Tv of each codon position showed that the third positions were highly saturated by multiple substitutions. Maximum parsimony analysis produced two groups: (1) I. typographus, I. cembrae, I. amitinus, I. duplicatus and I. acuminatus; (2) I. mannsfeldi, I. sexdentatus and the two outgroups. In all analyses the species of the first cluster were put together and I. typographus and I. cembrae, and I. mannsfeldi and O. erosus emerged as sister pairs. The data do not support a common ancestor for the seven European lps species. The eight-spined bark beetles (except I. mannsfeldi) and I. acuminatus formed a monophyletic group. The close relationship of I. mannsfeldi and O. erosus supports the latter belonging to the genus lps as proposed by Wood (1982) and Escherich (1923). However, more genetic markers and more species of the genera Orthotomicus and Pityokteines have to be analysed to resolve the phylogenetic positions of I. sexdentatus I. mannsfeldi within the tribe lpinl.
Insect Mol Biol 1997 Aug
PMID:The phylogenetic relationships of seven European Ips (Scolytidae, Ipinae) species. 927 41

Clinical drug resistance, a common and compromising side-effect during anticancer chemotherapy, is an acquired cellular resistance simultaneously to several cytotoxic drugs. Expression of the multidrug resistance gene (mdr) is one of the most-studied potential underlying mechanisms. The human mdr gene family encompasses two homologous members, the first of which, called the mdr1 gene, is the best-characterized so far. The human mdr1 gene has been shown to encode a membrane P-170 glycoprotein that, on the basis of its structure, is considered to act as a drug-efflux pump excreting various drugs from cells. The human mdr1 gene is thus a major regulated gene playing an important role in the molecular mechanism of multidrug resistance. Its bipartite structure of two similarly organized halves is explained by a gene fusion event during evolution. However, the clinical significance of this particular feature, if it seemed obvious in the 1980s as a factor producing chemoresistance, is currently revised-being a marker of tumor aggressiveness rather than the cause of drug resistance.
Cytokines Cell Mol Ther 1997 Jun
PMID:Multidrug resistance: molecular and clinical aspects. 928 48

The ciliary neurotrophic factor (CNTF) can regulate survival and differentiation of many types of developing and adult neurons; in metastatic SK-N-BE neuroblastoma cells, it promotes differentiation and neurite outgrowth. The expression of Gelatinase A (MMP-2) and its specific tissue inhibitor (TIMP-2), a degradative system whose balance is involved in matrix invasion and metastasis, was investigated in SK-N-BE cells cultured with and without CNTF or NGF. Zymographic analysis of conditioned media revealed that the cells constitutively secrete two gelatinases, mainly pro-MMP-2 but also traces of pro-MMP-9. In a time-course experiment in the presence of 25 ng/ml of CNTF, the MMP-2 mRNA expression showed no significant modulation, while TIMP-2 mRNA up-regulated to > 2-fold after 48 h and then fell dramatically. At the same concentrations, NGF showed no effect. TIMP-2 mRNA expression showed a dose-dependent increase of up to 8-fold from 1 to 250 ng/ml of CNTF and increased secretion of TIMP-2 was confirmed by Western blotting. MMP-2 was only slightly over-expressed under the same conditions, at either mRNA or protein level, with no correlation with neurocytokine concentration. These results suggest that boosting the expression of TIMP-2 by CNTF could restrain both matrix degradation following nervous system injury and neuroblastoma aggressiveness.
Brain Res Mol Brain Res 1997 Aug
PMID:CNTF up-regulation of TIMP-2 in neuroblastoma cells. 937 46

The relationships between carcinomatous aggressiveness and the glucolytic metabolism, namely the rate of 14CO2 production from [U-14C] glucose, are obtained from human breast tissues using radiorespirometry. The values are estimated as the initial velocity (V) expressed in eta 14CO2 x min-1 x g-1 of fresh tissues by [U-14C] glucose metabolism. The aggressiveness of the breast carcinomatous is diagnosed by the SBR grade system. As two control normal tissues, (V) are 0.86 to 0.90 from non-cancer patients. In carcinomatous tissues (Vc), there is an increase from 1.53 to 3.14, but in the corresponding surrounding non-cancer tissues (Vn) these show a decrease from 2.20 to 0.22 for SBR I, SNR II to SBR III. The ratio between (Vc) and (Vn) are found, according to carcinomatous aggressiveness, as 1.45 to 1.54, 1.69, 2.35 to 2.86 and 4.82 to 10.38 respectively for SBR I, lobular carcinoma, SBR II and SBR III; while the ratio is 1.04 for the normal tissue which come from non-cancer patients. The above results suggest the possibility of assessing the carcinomatous aggressiveness by radiorespirometry before a histopathological diagnosis, even in a lower aggressiveness as in SBR I cases which are difficult to diagnose and manage.
Biochem Mol Biol Int 1998 Sep
PMID:A proposed estimate of the tumor aggressiveness of human breast cancer using radiorespirometry. 976 5

Telomerase maintains telomere length and is considered to be necessary for the indefinite proliferation of human cells. Telomerase activity is detected not only in germline and immortal cancer cells, but also in stem/progenitor cells of renewal tissues and activated lymphocytes. While it is generally agreed that telomerase is a useful tumor marker, the utility of telomerase activity in non-cancerous cells should also be considered. In the present study, we quantitatively examined telomerase activity in 56 cytology samples and 106 bronchoalveolar lavage samples obtained from patients with various respiratory diseases. Fourteen of 34 samples obtained from lung cancer patients showed detectable telomerase activity, while only 7 of 128 samples obtained from patients without lung cancer did (p<0.001). Moreover, 12 of 14 telomerase-positive samples with lung cancer showed strong signals, while none without lung cancer did. Among 106 non-cancerous bronchoalveolar lavage samples, 4 telomerase positive samples had increased number of lymphocytes and increased disease progression. These findings indicate that evaluation of telomerase activity may not only be a useful diagnostic test for lung cancer, but may also be a marker of disease aggressiveness for immune-associated lung diseases.
Int J Mol Med 1998 Mar
PMID:Telomerase activity as a novel marker of lung cancer and immune-associated lung diseases. 985 60

Background: Clinical stage at presentation and tumor status at second-look laparotomy are currently the best predictors of patient survival in epithelial ovarian carcinoma (EOC). Methods and Results: To evaluate the predictive value of genetic analysis, the presence and type of p53 mutation (p53 genotype) was determined in 76 patients treated for EOC between 1987 and 1992 and subjected to second-look laparotomy following initial treatment. Mutational analysis of p53 was performed retrospectively by means of topographic genotyping (TG), using formalin-fixed, paraffin-embedded tissue of the primary and recurrent tumor. In TG, minute tissue samples were dissected from unstained histologic sections, amplified for p53 exons 5-8 with the polymerase chain reaction (PCR), and then direct sequenced. The p53 genotype was correlated with tumor stage, histologic grade and type, tumor status at second look, and survival at 3 and 5 years. Mutational change involving p53 exons 5-8 was found in 41 of 76 tumors (54%), consisting of 29 cases manifesting missense alterations and 12 cases having truncations (deletions, insertions, or stop codons). Tumor mutational change for each patient was strictly limited to a single type, being identical in all recurrences of an individual primary cancer. Mutations of p53 were distributed over exons 5-8, with certain "hot spots" being evident (codons 220, 245, and 273). Mutational change was present in all stages of primary EOC, but was relatively more frequent in tumors of advanced stage (III and IV). Epithelial ovarian carcinoma manifesting p53 mutational damage was significantly more likely to show recurrence at second-look laparotomy (P <.001) and to have shorter survival at the 3- and 5-year follow-up (P <.001) evaluation. The predictive value of p53 genotype was independent of stage at presentation, histologic grade, or histopathologic type. Conclusions: Genotyping of p53 provides useful information on tumor aggressiveness and is an informative predictive marker of biologic tumor behavior, treatment response, and survival in EOC.
Mol Diagn 1996 Jun
PMID:Relationship of p53 Genotype to Second-look Recurrence and Survival in Ovarian Epithelial Malignancy. 1033 Feb 7

In neuroblastoma, a childhood tumor of neural crest, a tumor suppressor gene located at 1p36 has been implicated to play a major role in tumor aggressiveness and clinical prognosis. We have examined 30 different staged primary neuroblastoma tumors using RT-PCR, for expression of the p73 gene located at 1p36.3, and its correlation to other clinical and biological features of these tumors. No correlation between expression of p73 and MYCN-amplification or 1p-deletion could be found, five of ten 1p-deleted tumors showed detectable levels of p73, and no mutations could be detected, neither in the retained alleles nor in any other parts of the material. In five 1p-deleted cases the origin of deletion were determined, two were of maternal and three of paternal origin. Both tumors with maternal 1p-loss showed detectable levels of p73, whereas the three with paternal loss did not. This suggests that p73 is expressed from the paternal allele only in advanced staged neuroblastoma tumors. Furthermore, it suggests absence of correlation between p73-expression and stage in these tumors. In conclusion, we could find no evidence for p73 being the neuroblastoma tumor suppressor gene in 1p36.
Int J Mol Med 1999 Jun
PMID:Variable expression and absence of mutations in p73 in primary neuroblastoma tumors argues against a role in neuroblastoma development. 1034 Dec 87

Anthracnose, one of the most important diseases of common bean (Phaseolus vulgaris), is caused by the fungus Colletotrichum lindemuthianum. A "candidate gene" approach was used to map anthracnose resistance quantitative trait loci (QTL). Candidate genes included genes for both pathogen recognition (resistance genes and resistance gene analogs [RGAs]) and general plant defense (defense response genes). Two strains of C. lindemuthianum, identified in a world collection of 177 strains, displayed a reproducible and differential aggressiveness toward BAT93 and JaloEEP558, two parental lines of P. vulgaris representing the two major gene pools of this crop. A reliable test was developed to score partial resistance in aerial organs of the plant (stem, leaf, petiole) under controlled growth chamber conditions. BAT93 was more resistant than JaloEEP558 regardless of the organ or strain tested. With a recombinant inbred line (RIL) population derived from a cross between these two parental lines, 10 QTL were located on a genetic map harboring 143 markers, including known defense response genes, anthracnose-specific resistance genes, and RGAs. Eight of the QTL displayed isolate specificity. Two were co-localized with known defense genes (phenylalanine ammonia-lyase and hydroxyproline-rich glycoprotein) and three with anthracnose-specific resistance genes and/or RGAs. Interestingly, two QTL, with different allelic contribution, mapped on linkage group B4 in a 5.0 cM interval containing Andean and Mesoamerican specific resistance genes against C. lindemuthianum and 11 polymorphic fragments revealed with a RGA probe. The possible relationship between genes underlying specific and partial resistance is discussed.
Mol Plant Microbe Interact 2000 Mar
PMID:Inheritance of partial resistance against Colletotrichum lindemuthianum in Phaseolus vulgaris and co-localization of quantitative trait loci with genes involved in specific resistance. 1070 54

The helix-loop-helix protein Id-1 inhibits the activity of basic helix-loop-helix transcription factors, and is an important regulator of cell growth and tissue-specific differentiation. We have shown (P. Y. Desprez et al., Mol. Cell. Biol., 18: 4577-4588, 1998) that ectopic expression of Id-1 inhibits differentiation and stimulates the proliferation and invasiveness of mouse mammary epithelial cells, and that there is a correlation between the levels of Id-1 protein and the aggressiveness of several human breast cancer cell lines. Here, we show that aggressive and metastatic breast cancer cells express high levels of Id-1 mRNA because of a loss of serum-dependent regulation that is mediated by a 2.2-kb region of the human Id-1 promoter. Three lines of evidence suggest that unregulated Id-1 expression may be an important regulator of the aggressive phenotype of a subset of human breast cancer cells: (a) a constitutively expressed Id-1 cDNA, when introduced into a nonaggressive breast cancer cell line (T47D), conferred a more aggressive phenotype, as measured by growth and invasiveness; (b) Id-1 was an important mediator of the effects of sex steroid hormones on T47D cell proliferation. Estrogen stimulated proliferation and induced Id-1 expression, whereas progesterone inhibited proliferation and repressed Id-1 expression. Progesterone repressed Id-1 expression, at least in part by repressing transcription. Most importantly, an antisense oligonucleotide that reduced Id-1 protein levels reduced the ability of estrogen to stimulate cell proliferation, whereas constitutive Id-1 expression rendered cells refractory to growth inhibition by progesterone; and (c) using a limited number of breast cancer biopsies, we showed that Id-1 was more frequently expressed in infiltrating carcinomas compared with ductal carcinomas in situ. Our results suggest that Id-1 can control the malignant progression of breast cancer cells, particularly that mediated by sex steroid hormones. Moreover, Id-1 has the potential to serve as a marker for aggressive breast tumors.
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PMID:A role for Id-1 in the aggressive phenotype and steroid hormone response of human breast cancer cells. 1072 95


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