ELIZA

return kwic search for show out of >500 occurrences
663834 occurrences (No.9 in the rank) during 5 years in the PubMed. [no cache] 500 found

26) Together, we show that Notch2 mediates differentiation and has tumor suppressor functions during lung carcinogenesis, whereas Notch1 promotes tumor initiation and progression.

--- ABSTRACT ---

PMID:24509876 DOI:10.1038/onc.2013.592

2015 Oncogene

* Opposing role of Notch1 and Notch2 in a Kras(G12D)-driven murine non-small cell lung cancer model.

- Lung cancer is the leading cause of cancer-related deaths worldwide. Recently, we have shown that Notch1 inhibition resulted in substantial cell death of non-small cell lung cancer (NSCLC) cells in vitro. New compounds targeting Notch signal transduction have been developed and are now being tested in clinical trials. However, the tumorigenic role of individual Notch receptors in vivo remains largely unclear. Using a Kras(G12D)-driven endogenous NSCLC mouse model, we analyzed the effect of conditional Notch1 and Notch2 receptor deletion on NSCLC tumorigenesis. Notch1 deficiency led to a reduced early tumor formation and lower activity of MAPK compared with the controls. Unexpectedly, Notch2 deletion resulted in a dramatically increased carcinogenesis and increased MAPK activity. These mice died significantly earlier due to rapidly growing tumor burden. We found that Notch1 regulates Ras/MAPK pathway via HES1-induced repression of the DUSP1 promoter encoding a phosphatase specifically suppressing pERK1/2. Interestingly, Notch1 but not Notch2 ablation leads to decreased HES1 and DUSP1 expression. However, Notch2-depleted tumors showed an appreciable increase in β-catenin expression, a known activator of HES1 and important lung cancer oncogene. Characteristically for β-catenin upregulation, we found that the majority of Notch2-deficient tumors revealed an undifferentiated phenotype as determined by their morphology, E-Cadherin and TTF1 expression levels. In addition, these carcinomas showed aggressive growth patterns with bronchus invasion and obstruction. Together, we show that Notch2 mediates differentiation and has tumor suppressor functions during lung carcinogenesis, whereas Notch1 promotes tumor initiation and progression. These data are further supported by immunohistochemical analysis of human NSCLC samples showing loss or downregulation of Notch2 compared with normal lung tissue. In conclusion, this is the first study characterizing the in vivo functions of Notch1 and Notch2 in Kras(G12D)-driven NSCLC tumorigenesis. These data highlight the clinical importance of a thorough understanding of Notch signaling especially with regard to Notch-targeted therapies.

--- ABSTRACT END ---

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(1)255 that	(9)5 here	(17)3 different	(25)2 differences
(2)30 a	(10)5 promise	(18)3 risk	(26)2 differential
(3)24 the	(11)4 by	(19)3 statistically	(27)2 for
(4)13 how	(12)4 greater	(20)3 such	(28)2 great
(5)13 significant	(13)4 higher	(21)2 null	(29)2 important
(6)8 any	(14)4 increased	(22)2 beneficial	(30)2 lower
(7)8 that,	(15)4 more	(23)2 changes
(8)7 an	(16)4 similar	(24)2 clinical

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--- WordNet output for show --- =>教える, 見せること, 展覧会, 見世物, 外観, を見せる, を案内する, を明らかにする, 見える Overview of noun show The noun show has 4 senses (first 2 from tagged texts) 1. (18) show -- (the act of publicly exhibiting or entertaining; "a remarkable show of skill") 2. (9) display, show -- (something intended to communicate a particular impression; "made a display of strength"; "a show of impatience"; "a good show of looking interested") 3. show -- (a social event involving a public performance or entertainment; "they wanted to see some of the shows on Broadway") 4. appearance, show -- (pretending that something is the case in order to make a good impression; "they try to keep up appearances"; "that ceremony is just for show") Overview of verb show The verb show has 12 senses (first 11 from tagged texts) 1. (136) show, demo, exhibit, present, demonstrate -- (give an exhibition of to an interested audience; "She shows her dogs frequently"; "We will demo the new software in Washington") 2. (63) prove, demonstrate, establish, show, shew -- (establish the validity of something, as by an example, explanation or experiment; "The experiment demonstrated the instability of the compound"; "The mathematician showed the validity of the conjecture") 3. (57) testify, bear witness, prove, evidence, show -- (provide evidence for; "The blood test showed that he was the father"; "Her behavior testified to her incompetence") 4. (43) show -- (make visible or noticeable; "She showed her talent for cooking"; "Show me your etchings, please") 5. (32) picture, depict, render, show -- (show in, or as in, a picture; "This scene depicts country life"; "the face of the child is rendered with much tenderness in this painting") 6. (24) express, show, evince -- (give expression to; "She showed her disappointment") 7. (24) indicate, point, designate, show -- (indicate a place, direction, person, or thing; either spatially or figuratively; "I showed the customer the glove section"; "He pointed to the empty parking space"; "he indicated his opponents") 8. (11) show, show up -- (be or become visible or noticeable; "His good upbringing really shows"; "The dirty side will show") 9. (7) read, register, show, record -- (indicate a certain reading; of gauges and instruments; "The thermometer showed thirteen degrees below zero"; "The gauge read `empty'") 10. (6) show -- (give evidence of, as of records; "The diary shows his distress that evening") 11. (2) usher, show -- (take (someone) to their seats, as in theaters or auditoriums; "The usher showed us to our seats") 12. show -- (finish third or better in a horse or dog race; "he bet $2 on number six to show") --- WordNet end ---