Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

NRH:Quinone oxidoreductase 2 (NQO2) is an enzyme that catalyzes the reductive metabolism of quinones. C57BL/6 NQO2-/- mice lacking NQO2 gene expression were generated in our laboratory. The dorsal skin of NQO2-deficient mice was exposed to 7,12-dimethylbenz(a)anthracene (DMBA) or benzo(a)pyrene alone (complete carcinogen) or with 12-O-tetradecanoylphorbol-13-acetate (TPA) (initiation/promotion model) to determine the in vivo role of NQO2 in chemical carcinogenesis. The NQO2-/- mice showed significantly increased tumor frequency with DMBA + TPA when compared with their wild-type littermates. The benzo(a)pyrene + TPA also showed increase in tumor incidence in NQO2-/- mice but to a less extent than DMBA. DMBA alone resulted in low frequency of tumor development with no difference in susceptibility between wild-type and NQO2-/- mice. Benzo(a)pyrene alone failed to induce tumors in either wild-type or NQO2-/- mice. Histologic analysis of the NQO2-/- mice tumors demonstrated proliferative activity. The treatment of NQO2-/- mice skin with benzo(a)pyrene failed to significantly increase tumor suppressor protein p53 and p53-regulated growth-related protein p21 and proapoptotic protein Bax as observed in case of wild-type mice. These results demonstrate that NQO2 protects against DMBA- and benzo(a)pyrene-induced skin carcinogenesis and suggest that NQO2 protection might be against tumor promotion. The results also suggest that lack of induction of p53, p21, and Bax proteins might contribute to increased sensitivity of NQO2-/- mice skin to benzo(a)pyrene carcinogenicity.
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PMID:Deficiency of NRH:quinone oxidoreductase 2 increases susceptibility to 7,12-dimethylbenz(a)anthracene and benzo(a)pyrene-induced skin carcinogenesis. 3283 29

The homeotic gene HOXA5 has been shown to play an important role in breast tumorigenesis. We have shown that loss of p53 correlated with loss of a developmentally regulated transcription factor, HOXA5, in primary breast cancer. Searching for potential protein interacting partners we found that HOXA5 binds to an anti-apoptotic protein, Twist. Furthermore, Twist-overexpressing MCF-7 cells displayed a deregulated p53 response to gamma-radiation and decreased regulation of downstream target genes. Using a p53-promoter-reporter system, we demonstrated that HOXA5 could partially restore the inhibitory effects of Twist on p53 target genes. These effects are likely mediated through both the transcriptional up-regulation of p53 and the protein-protein interaction between HOXA5 and Twist. Thus, the loss of HOXA5 expression could lead to the functional activation of Twist resulting in aberrant cell cycle regulation and promoting breast carcinogenesis.
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PMID:HOXA5-twist interaction alters p53 homeostasis in breast cancer cells. 1554 68

Yuk-Hap-Tang (YHT) induces cell death in human cervical carcinoma HeLa cells. Caspase-3, -6 and -9 were markedly activated in HeLa cells treated with YHT. The preferred substrate for caspase-3 cysteine protease, PARP, was cleaved to its 85-kDa cleavage product. YHT increased the amount of the anti-apoptotic protein, Bcl-2, and the pro-apoptotic protein, Bax. Although p53 has been reported to accumulate in cancer cells in response to anticancer agents, the p53 expression level was not changed in HeLa cells treated with YHT. Manganese (Mn)-TBAP, a mitochondria-specific SOD mimetic agent and NAC/GSH (N-acetyl cysteine/ reduced glutathione) reduced the YHT-induced cytotoxicity and decreased the number of the YHT-induced apoptotic cells. Furthermore, YHT reduced the expression of Mn-SOD protein and its activity in HeLa cells. The data demonstrate that YHT induces the apoptosis of human cervical carcinoma HeLa cells by intervening Mn-SOD.
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PMID:Yuk-Hap-Tang induces apoptosis by intervening mn-SOD in human cervical carcinoma HeLa cells. 1567 94

We previously demonstrated that evodimine isolated from Evodia rutaecarpa (Goshuyu in Japan) induced apoptosis in human malignant melanoma A375-S2 cells within 24 h. In this study, TUNEL assay also indicated that one cause of A375-S2 cell death induced by evodiamine was apoptosis. After treatment with evodiamine for the indicated time periods, anti-apoptotic protein SIRT1 expression was decreased; p53 expression and its phosphorylation were both enhanced, whereas transient induction of downstream p21 was not enough to promote cell cycle arrest. Inhibition of the phosphoinositide 3-OH kinase (PI3-K)/protein kinase C (PKC) survival pathway as well as subsequent inhibition of the ERK cascade might contribute to evodiamine-induced cell death. In addition, p53 activation in response to evodiamine administration was correlated with the activation of the PI3-K/PKC pro-apoptotic pathway, but did not require ERK participation. The inhibition of the PI3-K/PKC survival pathway might be responsible for SIRT1 inactivation and increased Bax/Bcl-2 expression ratio in evodiamine-induced cell death.
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PMID:Roles of SIRT1 and phosphoinositide 3-OH kinase/protein kinase C pathways in evodiamine-induced human melanoma A375-S2 cell death. 1582 41

There has been growing evidence that different modes of cell death exist, among them the apoptosis is thought to be an important mechanism of nerve cell loss implicated in various pathological states. A number of proteins mediated with apoptotic process have been identified, including p53, BAX, BCL-2 and BCL-X. We examined the expression of proteins related to programmed cell death in hippocampal neurons in vitro, exposed to pure anoxia or pretreated with apoptosis modulating agents: zinc and zinc chelator - TPEN. The results evidenced the noticeable differences in the expression of pro- and anti-apoptotic proteins in particular experiments. In the cultures exposed to pure anoxia, a significant increase of p53 and BAX immunoreactivity, associated with the decreased level of BCL-2 and BCL-X immunopositive cells was observed, related to the activation of apoptotic process. Hippocampal cultures pretreated with ZnCl2 before anoxia showed decreased immunoreactivity for p53 and BAX, connected with BCL-2 overexpression, whereas the cultures exposed to zinc chelating agent - TPEN or TPEN connected with anoxia showed significant increase of immunorectivity for p53 and BAX. This strong immunoreactivity of proapototic proteins (p53 and BAX) in hippocampal cultures exposed to anoxia or/and TPEN correlated with previous ultrastructural evidences of anoxia- and TPEN-induced apoptosis, while the overexpression of anti-apoptotic protein (BCL-2 and BCL-X) in zinc-pretreated cultures evidenced the protective ability of this metal against apoptosis in model of anoxia in vitro.
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PMID:Expression of apoptosis-related proteins in model of anoxia in vitro. 1582 87

The aim of this study was to discuss the relevance of the Epstein-Barr virus (EBV) in the nasopharyngeal carcinoma (NPC), analyzing the variations of several molecules potentially involved in the pathogenesis of this cancer. EBV was detected in all the NPC samples by several techniques including PCR, in situ hybridization, and immunohistochemical methodologies. CD21 membrane receptor was absent after EBV infection, being a differential morphological feature of the tumoral cells. Latent membrane protein-1 (LMP1), an oncogenic viral product, was detected in a high percentage of samples, supporting a role for EBV in the pathogenesis of NPC. Bcl-2, an anti-apoptotic protein up-regulated by LMP1, was also overexpressed, coinciding with the majority of samples positive for LMP1. Finally, p53 presented abnormalities only in a low percentage of samples. These results reinforce the role of the EBV in the NPC discussing several potential mechanisms of pathogenesis in this neoplasia.
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PMID:Involvement of the Epstein-Barr virus in the nasopharyngeal carcinoma pathogenesis. 1596 73

Endometrial adenocarcinoma is the most common malignant neoplasm of the female genital tract and, despite its relative frequency, the molecular events that contribute to the development and progression of the lesion remain poorly understood. The normal human endometrium is characterized by hormone-dependent variations during the menstrual cycle. This tightly controlled system is disturbed in endometrial hyperplasia and carcinomas and a series of changes initiate and promote progression towards the malignant phenotype. These changes can be subdivided into discrete steps, involving activation of oncogenes, inactivation of tumour suppressor genes, deregulation of cell cycle regulators or other proteins involved in tumour invasion and progression. Immunohistochemical expression of different biomarkers such as hormone receptor status (ER, PR), proliferation associated indices (PCNA, MIB1), oncogene (c-erbB-2), tumour suppressor gene products (pRb, p53 protein), cell cycle related proteins (cyclin D1, cyclin E, p21/WAF1), anti-apoptotic protein (bcl-2), adhesion molecule (CD44s), proteolytic enzyme (cathepsin D), heat shock protein (hsp27) and metallothionein (MT) has shown the contribution of these molecules to endometrial carcinogenesis in a hormone-dependent or independent manner as an early or late event. In addition, these biomarkers seem to be correlated with tumour differentiation or myometrial invasion, and therefore could be considered as indicators of the biological behaviour of endometrial carcinoma. Furthermore, the interrelationships of these molecular markers show that these genetic dysregulations could be implicated in the control of cell proliferation and differentiation, and thereby in the multistep process of endometrial carcinogenesis.
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PMID:Immunohistochemical tumour markers in endometrial carcinoma. 1612 80

The majority of human prostate cancers arise from the peripheral zone (PZ). Prostate epithelial stem cells have been localized to the basal epithelial cell compartment. In addition, basal cells have been shown to maintain luminal epithelial cell differentiation and may mediate signals between the stromal and luminal cell compartments. Therefore, the study of adult prostate basal cells derived from different prostate zones may give insights into the mechanisms underlying normal and abnormal prostate growth. We herein compare the basal and sex steroid-stimulated expression and activity of several genes/proteins that are known to be critical in prostate cancer development in primary cultures of basal cells derived from the transition zone (TZ) and PZ of prostatectomy specimens. Our results demonstrate that prostate basal cells derived from the PZ versus TZ are more viable in culture, particularly in response to sex steroid addition. PZ cells exhibit higher telomerase activity and increased expression levels of androgen receptor, the anti-apoptotic protein bcl-2, and the dominant-negative splice variant of Kruppel-like Factor 6. PZ cells have lower basal expression levels of estrogen receptor-beta, the pro-apoptotic protein Bax, and cell-cycle inhibitor proteins (p53, p21(waf1/Cip1)). Finally, we demonstrate divergent responses to sex hormones in the two basal cell populations. The gene expression pattern in the PZ cells may partially explain the predominance of prostate cancer development in this region.
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PMID:Sex steroids have differential effects on growth and gene expression in primary human prostatic epithelial cell cultures derived from the peripheral versus transition zones. 1612 18

Xanthorrhizol is a sesquiterpenoid compound extracted from Curcuma xanthorrhiza, which is known locally as Temulawak. Traditionally, C. xanthorrhiza was found to have antibacterial, anticancer and anti-inflammatory activity. The rhizome has also been used to treat inflammation in postpartum uterine bleeding. An antiproliferative assay using methylene blue staining revealed that xanthorrhizol inhibited the proliferation of the cervical cancer cell line HeLa with an EC50 value of 6.16 microg/ml. Xanthorrhizol significantly increased apoptosis in HeLa cells, as evaluated by the Tdt-mediated dUTP nick end-labelling (TUNEL) assay and nuclear morphology by Hoechst 33258 staining. Western blot analysis, which was further confirmed by the immunostaining results, implied an up-regulation of tumor suppressor protein p53 and the pro-apoptotic protein Bax, following the treatment with xanthorrhizol. Xanthorrhizol, however, did not affect the expression of the anti-apoptotic protein, Bcl-2 and the viral oncoprotein, E6. Hence, xanthorrhizol is a promising antiproliferative and anticancer agent which induces p53 and Bax-dependent apoptosis in HeLa cervical cancer cells.
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PMID:Xanthorrhizol induces apoptosis via the up-regulation of bax and p53 in HeLa cells. 1615 67

Apoptin, a protein encoded by an avian virus, induces apoptosis in a tumor-specific way, acts p53-independently and is even stimulated by the anti-apoptotic protein Bcl-2. Activation of upstream caspases is not required, whereas the activation of downstream caspases is involved in rapid Apoptin-induced cell death. Yet, in a caspase-3-negative human breast cancer cell line, Apoptin can induce apoptosis, but delayed. These features indicate that Apoptin can induce apoptosis via multiple pathways in tumor cells when other agents might fail. Apoptin is biologically active as a highly stable, multimeric complex, consisting of 30 to 40 monomers and forms cooperatively distinct superstructures upon binding to DNA. In tumor cells, Apoptin is imported into the nucleus prior to the induction of apoptosis; this contrasts with the situation in primary, normal cell cultures where nuclear import of Apoptin is very rare. Apoptin contains two different domains that induce apoptosis independently, and for both domains, a strong correlation exists between nuclear localization and killing activity. Apoptin is regulated by a kinase activity present in cancer cells but negligible in normal cells. Apoptin interacts with various partners of the human proteome such as DEDAF, which when overexpressed induces apoptosis in various human tumor cell lines but not in primary human cells, similar to Apoptin. In normal cells, Apoptin becomes aggregated, epitope shielded and eventually degraded in the cytoplasm. Furthermore, Apoptin-transgenic mice and other animal models have revealed Apoptin as a safe and efficient anti-tumor agent. These in vitro and in vivo tumor-specific features of Apoptin imply that it can form the basis of future anti-tumor therapies.
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PMID:Apoptin acts as a tumor-specific killer: potentials for an anti-tumor therapy. 1617 64


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