<i>PIG7/LITAF</i> gene mutation and overexpression of its gene product in extramammary Paget's disease

Matsumura, Yasuhiro; Matsumura, Yasuhiro; Nishigori, Chikako; Horio, Takeshi

doi:10.1002/ijc.20251

Cited by 17 publications

(15 citation statements)

References 21 publications

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“…Furthermore, LITAF/ PIG7 has been found to be involved in the carcinogenesis of extramammary Paget's disease (29); therefore, further investigation is warranted to determine whether this short 7-amino-acid p53 peptide (KQSQHMT) plays an important role in p53-regulated LITAF-mediated processes. Taken together, our findings highlight the influence of a 7-amino-acid p53 peptide that binds specifically and with high affinity to the LITAF promoter.…”

Section: Discussionmentioning

confidence: 99%

p53 Short Peptide (p53pep164) Regulates Lipopolysaccharide-Induced Tumor Necrosis Factor-α Factor/Cytokine Expression

2007

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The p53 protein is a sequence-specific DNA-binding factor that can induce apoptosis or activate genes whose dysregulation is involved in cancer. By using serial analysis of gene expression technique, p53-induced genes (PIGs) have been identified, one of which was lipopolysaccharide (LPS)-induced tumor necrosis factor-A (TNF-A) factor (LITAF/ PIG7). LITAF regulates the transcription of cytokines such as TNF-A. To further elucidate the role of p53 in LITAF expression, LITAF promoter activity was carefully dissected. In this study, we found that the element required for transcriptional activity is mainly located in the region from À990 to À500 of the LITAF promoter; the specific site required for p53 protein-DNA binding is located between À550 and À500. We also found that transient transfection of either a p53 short DNA sequence, called p53LFB12, or its corresponding 7-amino-acid synthetic peptide from amino acids 164 to 170 (K164Q165S166Q167H168M169T170), named p53pep164, significantly reduced LITAF promoter activity to 15% in p53-null H1299 cells. Transfection of p53pep164 into H1299 cells significantly down-regulated LPS-induced LITAF expression as well. Furthermore, transfection of p53pep164 into human monocytes resulted in down-regulation of nine proinflammatory cytokines, including TNF-A. We also found that the LPS-activated p53 is a short-lived protein, and that p53-orchestrated apoptosis occurs shortly after the initiation stage following LPS stimulation and lasts a short time. Once p53 levels return to baseline, the p53-mediated inhibition of LITAF is released, and LITAF-mediated cytokine production can proceed. The present finding proposes a novel link between p53 and the inflammatory processes and highlights potential interventional approaches to control p53-associated inflammatory processes.

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Section: Discussionmentioning

confidence: 99%

p53 Short Peptide (p53pep164) Regulates Lipopolysaccharide-Induced Tumor Necrosis Factor-α Factor/Cytokine Expression

2007

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“…The other important proteins showing more than 4-fold increase in transcript expression in response to L-menthol (Supplementary Table S2) and reported earlier to be regulating apoptosis are CAPN1 (Piñeiro et al, 2007), NGFRAP1 (Naderi et al, 2007), ADAM17 (Wang et al, 2011), BAD (Adachi et al, 2002, PIG7 (Matsumura et al, 2004), and ILF1 (Sadkowski et al, 2008). Taxol induces CASP3-independent apoptosis in NIH3T3 cells by a calpain (CAPN1)-mediated mechanism (Piñeiro et al, 2007).…”

Section: Discussionmentioning

confidence: 87%

Repurposing L-Menthol for Systems Medicine and Cancer Therapeutics? L-Menthol Induces Apoptosis through Caspase 10 and by Suppressing HSP90

Faridi

Dhawan

Pal

et al. 2016

OMICS: A Journal of Integrative Biology

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The objective of the present study was to repurpose L-menthol, which is frequently used in oral health and topical formulations, for cancer therapeutics. In this article, we argue that monoterpenes such as L-menthol might offer veritable potentials in systems medicine, for example, as cheaper anti-cancer compounds. Other monoterpenes such as limonene, perillyl alcohol, and geraniol have been shown to induce apoptosis in various cancer cell lines, but their mechanisms of action are yet to be completely elucidated. Earlier, we showed that L-menthol modulates tubulin polymerization and apoptosis to inhibit cancer cell proliferation. In the present report, we used an apoptosis-related gene microarray in conjunction with proteomics analyses, as well as in silico interpretations, to study gene expression modulation in human adenocarcinoma Caco-2 cell line in response to L-menthol treatment. The microarray analysis identified caspase 10 as the important initiator caspase, instead of caspase 8. The proteomics analyses showed downregulation of HSP90 protein (also corroborated by its low transcript abundance), which in turn indicated inhibition of AKT-mediated survival pathway, release of pro-apoptotic factor BAD from BAD and BCLxL complex, besides regulation of other factors related to apoptosis. Based on the combined microarray, proteomics, and in silico data, a signaling pathway for L-menthol-induced apoptosis is being presented for the first time here. These data and literature analysis have significant implications for ''repurposing'' L-menthol beyond oral medicine, and in understanding the mode of action of plant-derived monoterpenes towards development of cheaper anticancer drugs in future.

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“…Over the last decade, several lines of evidence have indicated possible roles of PIG7 abnormality in pathogenesis of some malignancies, such as downregulated in the carcinoma of urinary bladder and breast cancer and 25,26 mutated in Paget's disease. 27 Upregulation of gene expression was also detected in methionine-induced apoptosis of melanoma cells. 26 PIG7 was silenced by homozygous deletion in primary mediastinal B-cell lymphoma and by promoter hypermethylation in germinal center lymphoma.…”

Section: Discussionmentioning

confidence: 96%

PIG7, transactivated by AML1, promotes apoptosis and differentiation of leukemia cells with AML1–ETO fusion gene

et al. 2011

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AML1, the potent transcription factor in hematopoiesis, is antagonized by AML1-ETO in t(8;21) leukemia. Our previous study showed that the differentiation and apoptosis of Kasumi-1 induced by sodium phenylbutyrate (PB), were accompanied by significant upregulation of PIG7 and AML1b (one of the AML1 isoforms). Here, we further investigated the relationship between AML1b and PIG7, also the effects of PIG7 on leukemia cells. The results demonstrated that exogenous AML1b could upregulate PIG7 expression in HEK-293 and CV-1 cells in sequence-specific and dosage-dependent manners, and this effect was antagonized by AML1-ETO. The specific AML1-binding site required for p53-induced gene 7 (PIG7) transactivation was located between nucleotides À1511 and À1503 in the PIG7 promoter. Overexpression of PIG7 could induce the apoptosis and differentiation of Kasumi-1 and SKNO-1 cells, but showed less effect on NB4 cells directly. Moreover, ectopic expression of PIG7 could sensitize these cell lines to PB or all-trans retinoic acid, respectively, which could then be abrogated by downregulation of PIG7 expression. Furthermore, the primary acute myeloid leukemia cells showed similar response to the ectopic expression of PIG7. In conclusion, PIG7 could be transactivated by AML1, which subsequently induces differentiation and apoptosis of leukemia cells, especially those with AML1-ETO fusion gene.

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PIG7/LITAF gene mutation and overexpression of its gene product in extramammary Paget's disease

Cited by 17 publications

References 21 publications

p53 Short Peptide (p53pep164) Regulates Lipopolysaccharide-Induced Tumor Necrosis Factor-α Factor/Cytokine Expression

p53 Short Peptide (p53pep164) Regulates Lipopolysaccharide-Induced Tumor Necrosis Factor-α Factor/Cytokine Expression

Repurposing L-Menthol for Systems Medicine and Cancer Therapeutics? L-Menthol Induces Apoptosis through Caspase 10 and by Suppressing HSP90

PIG7, transactivated by AML1, promotes apoptosis and differentiation of leukemia cells with AML1–ETO fusion gene

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