Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Excessive beta-catenin is considered to contribute to tumor progression by inducing transcription of cell cycle-related genes such as cyclin D1 and c-myc. In contrast, our recent studies demonstrated that beta-catenin could inhibit cell proliferation through activation of p14(ARF)/p53/p21(WAF1) pathway during trans-differentiation toward morular phenotype of endometrial carcinoma (Em Ca) cells. Here, we focused on associations with alterations in p16(INK4A) and pRb expression during this process. In clinical cases, p16(INK4A) immunoreactivity was found to frequently overlap with nuclear beta-catenin accumulation in small-sized morules and surrounding glandular carcinomas (Sur-Ca), demonstrating a significant positive correlation (r = 0.447, p < 0.0001) overall, while the immunoreactions showed stepwise decrease in enlarged morules, despite persistent accumulation of beta-catenin and p21(WAF1) in nuclei. Immunoreactivity for both total pRb and its phosphorylated form was apparently decreased in all morules as compared to Sur-Ca lesions, with a significantly positive correlation. In cell lines, transcriptional activation of p16(INK) (4A) promoter by active form beta-catenin, as well as p21(WAF1), occurred through the region from -385 to -280 bp relative to the translation start site, in a TCF4-independent manner. Moreover, cell proliferation was accompanied with phosphorylation of pRb and increased p16(INK4A) expression, while its inhibition by serum starvation caused decreased expression of total pRb but not p16(INK4A), resulting in high relative amounts of the latter. These findings indicate that induction of p16(INK4A) mediated by nuclear beta-catenin and p21(WAF1), along with loss of pRb expression, may be important for initial steps during trans-differentiation of Em Ca cells. In addition, its down-regulation is associated with progression of lesions.
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PMID:Induction of p16INK4A mediated by beta-catenin in a TCF4-independent manner: implications for alterations in p16INK4A and pRb expression during trans-differentiation of endometrial carcinoma cells. 1685 82

Nuclear beta-catenin is required for changes in morphology from glandular to morular phenotypes of endometrial carcinoma (Em Ca) cells, with activation of p14(ARF)/p53/p21(Waf1) and alteration of p16(INK4A)/pRb pathways. Having demonstrated previously that the homeodomain transcription factor Cdx2 increases markedly during intestinal epithelial cell differentiation, we have examined its effects in beta-catenin signaling during transdifferentiation of Em Ca cells. In clinical cases, Cdx2 immunoreactivity, along with increased mRNA signals, was found to overlap with nuclear accumulation of beta-catenin and p21(Waf1) in morules, demonstrating an inverse correlation with cell proliferation. In cell lines, over-expression of active form beta-catenin resulted in a significant increase in endogenous Cdx2 expression at both mRNA and protein levels. Furthermore, the Cdx2 promoter was activated by T-cell factor 4 (TCF4) -independent activated beta-catenin, as well as Cdx2 itself, through the region from -39 to +9 bp relative to transcription start site. Cells over-expressing exogenous Cdx2 showed high levels of p21(Waf1) expression due to stabilization of the mRNA status, resulting in significant decrease in the proliferation rate, in contrast to the lack of apparent changes in morphology. Moreover, transfected Cdx2 could inhibit beta-catenin/TCF4-mediated transcriptional activation of target genes, including p14(ARF) and cyclin D1, probably through indirect mechanisms. These data suggest that over-expression of Cdx2 mediated by nuclear beta-catenin and Cdx2 itself can cause an inhibition of Em Ca cell proliferation through up-regulation of p21(Waf1) expression, modulating beta-catenin/TCF4-mediated transcription. We therefore conclude that an association between Cdx2 and beta-catenin signaling may participate in induction of transdifferentiation of Em Ca cells.
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PMID:A functional role of Cdx2 in beta-catenin signaling during transdifferentiation in endometrial carcinomas. 1746 17

The malignant mesothelioma is an aggressive form of cancer with a mean survival rate of less than a year. Moreover, environmental exposure to minerals is an important factor in the development of malignant mesothelioma (MM), especially the mineral asbestos, which has a well-documented role in MM, and more recently, the mineral erionite has been proven to be a strong carcinogenic inducer of MM. In addition, the virus simian virus 40 has been implicated as a co-carcinogenic player in MM. However, the molecular mechanisms involved in the pathogenesis of this cancer are still not fully understood. Indeed, it is known that several genes are altered or mutated in MM, among those are p16(INK4A), p14(ARF), and neurofibromatosis type II. Furthermore, TP53 has been reported to be mutated in the majority of the cancers; however, in MM, it is very uncommon mutations in this gene. Also, the PTEN gene has been shown to play an important role in endometrial cancer and glioblastoma, although the role of PTEN in MM has yet to be established. Taken altogether, this review focuses on the historical aspects, molecular mechanisms, interaction with other genes and proteins, and the role of these genes in MM. Lastly, this review questions the cancer theory of the two hits because the functions of both PTEN and TP53 are not fully explained by this theory.
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PMID:The function, mechanisms, and role of the genes PTEN and TP53 and the effects of asbestos in the development of malignant mesothelioma: a review focused on the genes' molecular mechanisms. 2408 73