Transcriptome analysis reveals the essential role of NK2 homeobox 1/thyroid transcription factor 1 (NKX2-1/TTF-1) in gastric adenocarcinoma of fundic-gland type
Background Gastric adenocarcinoma of fundic-gland type (GA-FG) is a gastric malignancy with little relation to Helicobacter pylori . Clinical characteristics of GA-FG have been established, but molecular mechanisms leading to tumorigenesis have not yet been elucidated. Methods We subjected three GA-...
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| Veröffentlicht in: | Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2023-01, Vol.26 (1), p.44-54 |
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| creator | Fukagawa, Kazushi Takahashi, Yu Yamamichi, Nobutake Kageyama-Yahara, Natsuko Sakaguchi, Yoshiki Obata, Miho Cho, Rina Sakuma, Nobuyuki Nagao, Sayaka Miura, Yuko Tamura, Naoki Ohki, Daisuke Mizutani, Hiroya Yakabi, Seiichi Minatsuki, Chihiro Niimi, Keiko Tsuji, Yosuke Yamamichi, Mitsue Shigi, Narumi Tomida, Shuta Abe, Hiroyuki Ushiku, Tetsuo Koike, Kazuhiko Fujishiro, Mitsuhiro |
| description | Background
Gastric adenocarcinoma of fundic-gland type (GA-FG) is a gastric malignancy with little relation to
Helicobacter pylori
. Clinical characteristics of GA-FG have been established, but molecular mechanisms leading to tumorigenesis have not yet been elucidated.
Methods
We subjected three GA-FG tumors-normal mucosa pairs to microarray analysis. Network analysis was performed for the top 30 up-regulated gene transcripts, followed by immunohistochemical staining to confirm the gene expression analysis results. AGS and NUGC4 cells were transfected with the gene-encoding NK2 homeobox 1/thyroid transcription factor 1 (
NKX2-1/TTF-1
) to evaluate transcriptional changes in its target genes.
Results
Comprehensive gene expression analysis identified 1410 up-regulated and 1395 down-regulated gene probes with ≥ two-fold difference in expression. Among the top 30 up-regulated genes in GA-FG, we identified transcription factor NKX2-1/TTF-1, a master regulator of lung/thyroid differentiation, together with surfactant protein B (SFTPB), SFTPC, and secretoglobin family 3A member 2(SCGB3A2), which are regulated by NKX2-1/TTF-1. Immunohistochemical analysis of 16 GA-FG specimens demonstrated significantly higher NKX2-1/TTF-1 and SFTPB levels, as compared to that in adjacent normal mucosa (
P
|
| doi_str_mv | 10.1007/s10120-022-01334-5 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2713308835</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2760864313</sourcerecordid><originalsourceid>FETCH-LOGICAL-c536t-710582b7c4bc563bfb437da3df055d991b4c2bfbc681021be021c70453a56be13</originalsourceid><addsrcrecordid>eNp9kUFvFCEUx4nR2Lr6BTwYEi_tgS4PBmbmaBpbTZv2sibeCMMwuzQzsALTuN_GjyrrtjXpoRcg8OP3Xt4foY9Az4DSepmAAqOEMkYocF4R8QodQ8Ul4ZyK149n1sIRepfSHaUgWpBv0RGXtK1EK47Rn1XUPpnotjlMFmuvx11yCUd7b_WYcN5YbFOyPjs94hhGi8OAb64Y3hQ-dOE3hmXe7GJwPc5PLhc8HrTJIWLAJzdXPxmB5Wp1QeAUO4_XOuXoDNa99cHoaJwPk96bh9n3zpD1qH3x7bb2PXozlEbsh4d9gX5cfF2dfyPXt5ffz79cEyO4zKQGKhrW1abqjJC8G7qK173m_UCF6NsWusqwcmtkA5RBZ8tialoJroXsLPAFOjl4tzH8mm3KanLJ2LE0YsOcFKvLiGnTcFHQz8_QuzDHMrk9JWkjK17YBWIHysSQUrSD2kY36bhTQNU-P3XIT5X81L_81F796UE9d5Ptn748BlYAfgBSefJrG__XfkH7F0jNpaw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2760864313</pqid></control><display><type>article</type><title>Transcriptome analysis reveals the essential role of NK2 homeobox 1/thyroid transcription factor 1 (NKX2-1/TTF-1) in gastric adenocarcinoma of fundic-gland type</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>SpringerLink Journals - AutoHoldings</source><creator>Fukagawa, Kazushi ; Takahashi, Yu ; Yamamichi, Nobutake ; Kageyama-Yahara, Natsuko ; Sakaguchi, Yoshiki ; Obata, Miho ; Cho, Rina ; Sakuma, Nobuyuki ; Nagao, Sayaka ; Miura, Yuko ; Tamura, Naoki ; Ohki, Daisuke ; Mizutani, Hiroya ; Yakabi, Seiichi ; Minatsuki, Chihiro ; Niimi, Keiko ; Tsuji, Yosuke ; Yamamichi, Mitsue ; Shigi, Narumi ; Tomida, Shuta ; Abe, Hiroyuki ; Ushiku, Tetsuo ; Koike, Kazuhiko ; Fujishiro, Mitsuhiro</creator><creatorcontrib>Fukagawa, Kazushi ; Takahashi, Yu ; Yamamichi, Nobutake ; Kageyama-Yahara, Natsuko ; Sakaguchi, Yoshiki ; Obata, Miho ; Cho, Rina ; Sakuma, Nobuyuki ; Nagao, Sayaka ; Miura, Yuko ; Tamura, Naoki ; Ohki, Daisuke ; Mizutani, Hiroya ; Yakabi, Seiichi ; Minatsuki, Chihiro ; Niimi, Keiko ; Tsuji, Yosuke ; Yamamichi, Mitsue ; Shigi, Narumi ; Tomida, Shuta ; Abe, Hiroyuki ; Ushiku, Tetsuo ; Koike, Kazuhiko ; Fujishiro, Mitsuhiro</creatorcontrib><description>Background
Gastric adenocarcinoma of fundic-gland type (GA-FG) is a gastric malignancy with little relation to
Helicobacter pylori
. Clinical characteristics of GA-FG have been established, but molecular mechanisms leading to tumorigenesis have not yet been elucidated.
Methods
We subjected three GA-FG tumors-normal mucosa pairs to microarray analysis. Network analysis was performed for the top 30 up-regulated gene transcripts, followed by immunohistochemical staining to confirm the gene expression analysis results. AGS and NUGC4 cells were transfected with the gene-encoding NK2 homeobox 1/thyroid transcription factor 1 (
NKX2-1/TTF-1
) to evaluate transcriptional changes in its target genes.
Results
Comprehensive gene expression analysis identified 1410 up-regulated and 1395 down-regulated gene probes with ≥ two-fold difference in expression. Among the top 30 up-regulated genes in GA-FG, we identified transcription factor NKX2-1/TTF-1, a master regulator of lung/thyroid differentiation, together with surfactant protein B (SFTPB), SFTPC, and secretoglobin family 3A member 2(SCGB3A2), which are regulated by NKX2-1/TTF-1. Immunohistochemical analysis of 16 GA-FG specimens demonstrated significantly higher NKX2-1/TTF-1 and SFTPB levels, as compared to that in adjacent normal mucosa (
P
< 0.05), while SCGB3A2 levels did not differ (
P
= 0.341). Transduction of
NKX2-1/TTF-1
into AGS and NUGC4 cells induced transactivation of
SFTPB
and
SFTPC,
indicating that
NKX2-1/TTF-1
can function as normally in gastric cells as it can in the lung cells.
Conclusions
Our first transcriptome analysis of GA-FG indicates significant expression of NKX2-1/TTF1 in GA-FG. Immunohistochemistry and cell biology show ectopic expression and normal transactivation ability of NKX2-1/TTF-1, suggesting that it plays an essential role in GA-FG development.</description><identifier>ISSN: 1436-3291</identifier><identifier>EISSN: 1436-3305</identifier><identifier>DOI: 10.1007/s10120-022-01334-5</identifier><identifier>PMID: 36094595</identifier><language>eng</language><publisher>Singapore: Springer Nature Singapore</publisher><subject>Abdominal Surgery ; Adenocarcinoma ; Adenocarcinoma - genetics ; Adenocarcinoma - pathology ; Cancer ; Cancer Research ; DNA microarrays ; Ectopic expression ; Gastric cancer ; Gastroenterology ; Gene expression ; Gene Expression Profiling ; Genes, Homeobox ; Homeobox ; Humans ; Immunohistochemistry ; Malignancy ; Medicine ; Medicine & Public Health ; Molecular modelling ; Mucosa ; Oncology ; Original Article ; Protein B ; Stomach Neoplasms - genetics ; Stomach Neoplasms - pathology ; Surgical Oncology ; Thyroid gland ; Thyroid Nuclear Factor 1 - genetics ; Thyroid transcription factor 1 ; Transcription factors ; Transcriptomes ; Tumorigenesis</subject><ispartof>Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2023-01, Vol.26 (1), p.44-54</ispartof><rights>The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2022. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c536t-710582b7c4bc563bfb437da3df055d991b4c2bfbc681021be021c70453a56be13</citedby><cites>FETCH-LOGICAL-c536t-710582b7c4bc563bfb437da3df055d991b4c2bfbc681021be021c70453a56be13</cites><orcidid>0000-0002-3066-9501</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10120-022-01334-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10120-022-01334-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36094595$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fukagawa, Kazushi</creatorcontrib><creatorcontrib>Takahashi, Yu</creatorcontrib><creatorcontrib>Yamamichi, Nobutake</creatorcontrib><creatorcontrib>Kageyama-Yahara, Natsuko</creatorcontrib><creatorcontrib>Sakaguchi, Yoshiki</creatorcontrib><creatorcontrib>Obata, Miho</creatorcontrib><creatorcontrib>Cho, Rina</creatorcontrib><creatorcontrib>Sakuma, Nobuyuki</creatorcontrib><creatorcontrib>Nagao, Sayaka</creatorcontrib><creatorcontrib>Miura, Yuko</creatorcontrib><creatorcontrib>Tamura, Naoki</creatorcontrib><creatorcontrib>Ohki, Daisuke</creatorcontrib><creatorcontrib>Mizutani, Hiroya</creatorcontrib><creatorcontrib>Yakabi, Seiichi</creatorcontrib><creatorcontrib>Minatsuki, Chihiro</creatorcontrib><creatorcontrib>Niimi, Keiko</creatorcontrib><creatorcontrib>Tsuji, Yosuke</creatorcontrib><creatorcontrib>Yamamichi, Mitsue</creatorcontrib><creatorcontrib>Shigi, Narumi</creatorcontrib><creatorcontrib>Tomida, Shuta</creatorcontrib><creatorcontrib>Abe, Hiroyuki</creatorcontrib><creatorcontrib>Ushiku, Tetsuo</creatorcontrib><creatorcontrib>Koike, Kazuhiko</creatorcontrib><creatorcontrib>Fujishiro, Mitsuhiro</creatorcontrib><title>Transcriptome analysis reveals the essential role of NK2 homeobox 1/thyroid transcription factor 1 (NKX2-1/TTF-1) in gastric adenocarcinoma of fundic-gland type</title><title>Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association</title><addtitle>Gastric Cancer</addtitle><addtitle>Gastric Cancer</addtitle><description>Background
Gastric adenocarcinoma of fundic-gland type (GA-FG) is a gastric malignancy with little relation to
Helicobacter pylori
. Clinical characteristics of GA-FG have been established, but molecular mechanisms leading to tumorigenesis have not yet been elucidated.
Methods
We subjected three GA-FG tumors-normal mucosa pairs to microarray analysis. Network analysis was performed for the top 30 up-regulated gene transcripts, followed by immunohistochemical staining to confirm the gene expression analysis results. AGS and NUGC4 cells were transfected with the gene-encoding NK2 homeobox 1/thyroid transcription factor 1 (
NKX2-1/TTF-1
) to evaluate transcriptional changes in its target genes.
Results
Comprehensive gene expression analysis identified 1410 up-regulated and 1395 down-regulated gene probes with ≥ two-fold difference in expression. Among the top 30 up-regulated genes in GA-FG, we identified transcription factor NKX2-1/TTF-1, a master regulator of lung/thyroid differentiation, together with surfactant protein B (SFTPB), SFTPC, and secretoglobin family 3A member 2(SCGB3A2), which are regulated by NKX2-1/TTF-1. Immunohistochemical analysis of 16 GA-FG specimens demonstrated significantly higher NKX2-1/TTF-1 and SFTPB levels, as compared to that in adjacent normal mucosa (
P
< 0.05), while SCGB3A2 levels did not differ (
P
= 0.341). Transduction of
NKX2-1/TTF-1
into AGS and NUGC4 cells induced transactivation of
SFTPB
and
SFTPC,
indicating that
NKX2-1/TTF-1
can function as normally in gastric cells as it can in the lung cells.
Conclusions
Our first transcriptome analysis of GA-FG indicates significant expression of NKX2-1/TTF1 in GA-FG. Immunohistochemistry and cell biology show ectopic expression and normal transactivation ability of NKX2-1/TTF-1, suggesting that it plays an essential role in GA-FG development.</description><subject>Abdominal Surgery</subject><subject>Adenocarcinoma</subject><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - pathology</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>DNA microarrays</subject><subject>Ectopic expression</subject><subject>Gastric cancer</subject><subject>Gastroenterology</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Genes, Homeobox</subject><subject>Homeobox</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Malignancy</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Molecular modelling</subject><subject>Mucosa</subject><subject>Oncology</subject><subject>Original Article</subject><subject>Protein B</subject><subject>Stomach Neoplasms - genetics</subject><subject>Stomach Neoplasms - pathology</subject><subject>Surgical Oncology</subject><subject>Thyroid gland</subject><subject>Thyroid Nuclear Factor 1 - genetics</subject><subject>Thyroid transcription factor 1</subject><subject>Transcription factors</subject><subject>Transcriptomes</subject><subject>Tumorigenesis</subject><issn>1436-3291</issn><issn>1436-3305</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUFvFCEUx4nR2Lr6BTwYEi_tgS4PBmbmaBpbTZv2sibeCMMwuzQzsALTuN_GjyrrtjXpoRcg8OP3Xt4foY9Az4DSepmAAqOEMkYocF4R8QodQ8Ul4ZyK149n1sIRepfSHaUgWpBv0RGXtK1EK47Rn1XUPpnotjlMFmuvx11yCUd7b_WYcN5YbFOyPjs94hhGi8OAb64Y3hQ-dOE3hmXe7GJwPc5PLhc8HrTJIWLAJzdXPxmB5Wp1QeAUO4_XOuXoDNa99cHoaJwPk96bh9n3zpD1qH3x7bb2PXozlEbsh4d9gX5cfF2dfyPXt5ffz79cEyO4zKQGKhrW1abqjJC8G7qK173m_UCF6NsWusqwcmtkA5RBZ8tialoJroXsLPAFOjl4tzH8mm3KanLJ2LE0YsOcFKvLiGnTcFHQz8_QuzDHMrk9JWkjK17YBWIHysSQUrSD2kY36bhTQNU-P3XIT5X81L_81F796UE9d5Ptn748BlYAfgBSefJrG__XfkH7F0jNpaw</recordid><startdate>20230101</startdate><enddate>20230101</enddate><creator>Fukagawa, Kazushi</creator><creator>Takahashi, Yu</creator><creator>Yamamichi, Nobutake</creator><creator>Kageyama-Yahara, Natsuko</creator><creator>Sakaguchi, Yoshiki</creator><creator>Obata, Miho</creator><creator>Cho, Rina</creator><creator>Sakuma, Nobuyuki</creator><creator>Nagao, Sayaka</creator><creator>Miura, Yuko</creator><creator>Tamura, Naoki</creator><creator>Ohki, Daisuke</creator><creator>Mizutani, Hiroya</creator><creator>Yakabi, Seiichi</creator><creator>Minatsuki, Chihiro</creator><creator>Niimi, Keiko</creator><creator>Tsuji, Yosuke</creator><creator>Yamamichi, Mitsue</creator><creator>Shigi, Narumi</creator><creator>Tomida, Shuta</creator><creator>Abe, Hiroyuki</creator><creator>Ushiku, Tetsuo</creator><creator>Koike, Kazuhiko</creator><creator>Fujishiro, Mitsuhiro</creator><general>Springer Nature Singapore</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3066-9501</orcidid></search><sort><creationdate>20230101</creationdate><title>Transcriptome analysis reveals the essential role of NK2 homeobox 1/thyroid transcription factor 1 (NKX2-1/TTF-1) in gastric adenocarcinoma of fundic-gland type</title><author>Fukagawa, Kazushi ; Takahashi, Yu ; Yamamichi, Nobutake ; Kageyama-Yahara, Natsuko ; Sakaguchi, Yoshiki ; Obata, Miho ; Cho, Rina ; Sakuma, Nobuyuki ; Nagao, Sayaka ; Miura, Yuko ; Tamura, Naoki ; Ohki, Daisuke ; Mizutani, Hiroya ; Yakabi, Seiichi ; Minatsuki, Chihiro ; Niimi, Keiko ; Tsuji, Yosuke ; Yamamichi, Mitsue ; Shigi, Narumi ; Tomida, Shuta ; Abe, Hiroyuki ; Ushiku, Tetsuo ; Koike, Kazuhiko ; Fujishiro, Mitsuhiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c536t-710582b7c4bc563bfb437da3df055d991b4c2bfbc681021be021c70453a56be13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Abdominal Surgery</topic><topic>Adenocarcinoma</topic><topic>Adenocarcinoma - genetics</topic><topic>Adenocarcinoma - pathology</topic><topic>Cancer</topic><topic>Cancer Research</topic><topic>DNA microarrays</topic><topic>Ectopic expression</topic><topic>Gastric cancer</topic><topic>Gastroenterology</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Genes, Homeobox</topic><topic>Homeobox</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Malignancy</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Molecular modelling</topic><topic>Mucosa</topic><topic>Oncology</topic><topic>Original Article</topic><topic>Protein B</topic><topic>Stomach Neoplasms - genetics</topic><topic>Stomach Neoplasms - pathology</topic><topic>Surgical Oncology</topic><topic>Thyroid gland</topic><topic>Thyroid Nuclear Factor 1 - genetics</topic><topic>Thyroid transcription factor 1</topic><topic>Transcription factors</topic><topic>Transcriptomes</topic><topic>Tumorigenesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fukagawa, Kazushi</creatorcontrib><creatorcontrib>Takahashi, Yu</creatorcontrib><creatorcontrib>Yamamichi, Nobutake</creatorcontrib><creatorcontrib>Kageyama-Yahara, Natsuko</creatorcontrib><creatorcontrib>Sakaguchi, Yoshiki</creatorcontrib><creatorcontrib>Obata, Miho</creatorcontrib><creatorcontrib>Cho, Rina</creatorcontrib><creatorcontrib>Sakuma, Nobuyuki</creatorcontrib><creatorcontrib>Nagao, Sayaka</creatorcontrib><creatorcontrib>Miura, Yuko</creatorcontrib><creatorcontrib>Tamura, Naoki</creatorcontrib><creatorcontrib>Ohki, Daisuke</creatorcontrib><creatorcontrib>Mizutani, Hiroya</creatorcontrib><creatorcontrib>Yakabi, Seiichi</creatorcontrib><creatorcontrib>Minatsuki, Chihiro</creatorcontrib><creatorcontrib>Niimi, Keiko</creatorcontrib><creatorcontrib>Tsuji, Yosuke</creatorcontrib><creatorcontrib>Yamamichi, Mitsue</creatorcontrib><creatorcontrib>Shigi, Narumi</creatorcontrib><creatorcontrib>Tomida, Shuta</creatorcontrib><creatorcontrib>Abe, Hiroyuki</creatorcontrib><creatorcontrib>Ushiku, Tetsuo</creatorcontrib><creatorcontrib>Koike, Kazuhiko</creatorcontrib><creatorcontrib>Fujishiro, Mitsuhiro</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fukagawa, Kazushi</au><au>Takahashi, Yu</au><au>Yamamichi, Nobutake</au><au>Kageyama-Yahara, Natsuko</au><au>Sakaguchi, Yoshiki</au><au>Obata, Miho</au><au>Cho, Rina</au><au>Sakuma, Nobuyuki</au><au>Nagao, Sayaka</au><au>Miura, Yuko</au><au>Tamura, Naoki</au><au>Ohki, Daisuke</au><au>Mizutani, Hiroya</au><au>Yakabi, Seiichi</au><au>Minatsuki, Chihiro</au><au>Niimi, Keiko</au><au>Tsuji, Yosuke</au><au>Yamamichi, Mitsue</au><au>Shigi, Narumi</au><au>Tomida, Shuta</au><au>Abe, Hiroyuki</au><au>Ushiku, Tetsuo</au><au>Koike, Kazuhiko</au><au>Fujishiro, Mitsuhiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcriptome analysis reveals the essential role of NK2 homeobox 1/thyroid transcription factor 1 (NKX2-1/TTF-1) in gastric adenocarcinoma of fundic-gland type</atitle><jtitle>Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association</jtitle><stitle>Gastric Cancer</stitle><addtitle>Gastric Cancer</addtitle><date>2023-01-01</date><risdate>2023</risdate><volume>26</volume><issue>1</issue><spage>44</spage><epage>54</epage><pages>44-54</pages><issn>1436-3291</issn><eissn>1436-3305</eissn><abstract>Background
Gastric adenocarcinoma of fundic-gland type (GA-FG) is a gastric malignancy with little relation to
Helicobacter pylori
. Clinical characteristics of GA-FG have been established, but molecular mechanisms leading to tumorigenesis have not yet been elucidated.
Methods
We subjected three GA-FG tumors-normal mucosa pairs to microarray analysis. Network analysis was performed for the top 30 up-regulated gene transcripts, followed by immunohistochemical staining to confirm the gene expression analysis results. AGS and NUGC4 cells were transfected with the gene-encoding NK2 homeobox 1/thyroid transcription factor 1 (
NKX2-1/TTF-1
) to evaluate transcriptional changes in its target genes.
Results
Comprehensive gene expression analysis identified 1410 up-regulated and 1395 down-regulated gene probes with ≥ two-fold difference in expression. Among the top 30 up-regulated genes in GA-FG, we identified transcription factor NKX2-1/TTF-1, a master regulator of lung/thyroid differentiation, together with surfactant protein B (SFTPB), SFTPC, and secretoglobin family 3A member 2(SCGB3A2), which are regulated by NKX2-1/TTF-1. Immunohistochemical analysis of 16 GA-FG specimens demonstrated significantly higher NKX2-1/TTF-1 and SFTPB levels, as compared to that in adjacent normal mucosa (
P
< 0.05), while SCGB3A2 levels did not differ (
P
= 0.341). Transduction of
NKX2-1/TTF-1
into AGS and NUGC4 cells induced transactivation of
SFTPB
and
SFTPC,
indicating that
NKX2-1/TTF-1
can function as normally in gastric cells as it can in the lung cells.
Conclusions
Our first transcriptome analysis of GA-FG indicates significant expression of NKX2-1/TTF1 in GA-FG. Immunohistochemistry and cell biology show ectopic expression and normal transactivation ability of NKX2-1/TTF-1, suggesting that it plays an essential role in GA-FG development.</abstract><cop>Singapore</cop><pub>Springer Nature Singapore</pub><pmid>36094595</pmid><doi>10.1007/s10120-022-01334-5</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-3066-9501</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1436-3291 |
| ispartof | Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2023-01, Vol.26 (1), p.44-54 |
| issn | 1436-3291 1436-3305 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2713308835 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; SpringerLink Journals - AutoHoldings |
| subjects | Abdominal Surgery Adenocarcinoma Adenocarcinoma - genetics Adenocarcinoma - pathology Cancer Cancer Research DNA microarrays Ectopic expression Gastric cancer Gastroenterology Gene expression Gene Expression Profiling Genes, Homeobox Homeobox Humans Immunohistochemistry Malignancy Medicine Medicine & Public Health Molecular modelling Mucosa Oncology Original Article Protein B Stomach Neoplasms - genetics Stomach Neoplasms - pathology Surgical Oncology Thyroid gland Thyroid Nuclear Factor 1 - genetics Thyroid transcription factor 1 Transcription factors Transcriptomes Tumorigenesis |
| title | Transcriptome analysis reveals the essential role of NK2 homeobox 1/thyroid transcription factor 1 (NKX2-1/TTF-1) in gastric adenocarcinoma of fundic-gland type |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T16%3A56%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Transcriptome%20analysis%20reveals%20the%20essential%20role%20of%20NK2%20homeobox%201/thyroid%20transcription%20factor%201%20(NKX2-1/TTF-1)%20in%20gastric%20adenocarcinoma%20of%20fundic-gland%20type&rft.jtitle=Gastric%20cancer%20:%20official%20journal%20of%20the%20International%20Gastric%20Cancer%20Association%20and%20the%20Japanese%20Gastric%20Cancer%20Association&rft.au=Fukagawa,%20Kazushi&rft.date=2023-01-01&rft.volume=26&rft.issue=1&rft.spage=44&rft.epage=54&rft.pages=44-54&rft.issn=1436-3291&rft.eissn=1436-3305&rft_id=info:doi/10.1007/s10120-022-01334-5&rft_dat=%3Cproquest_cross%3E2760864313%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2760864313&rft_id=info:pmid/36094595&rfr_iscdi=true |