Functional analysis of clock genes in regulating the microenvironment of breast cancer

• Project/Area Number: 26870028
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology; General surgery
• Research Institution: Hirosaki University
• Principal Investigator: Wu Yunyan 弘前大学, 医学研究科, 助教 (40636586)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 時計遺伝子 / 乳腺 / 癌微小環境 / 血管新生

Outline of Final Research Achievements

We focused on analyzing the roles of clock genes in human breast cancer. The expression of DEC2 as well as the cell viability was upregulated when exposed MCF-7 cells to hypoxia (3% O2). Hypoxia caused the phosphorylation of Akt. DEC2 functioned as a target of the PI3K/Akt pathway and regulated the expression of c-Myc and contributed to the hypoxia-induced proliferation of MCF-7 cells.
In human esophageal carcinoma cells, DEC1 and DEC2 functioned as effectors of TGF-β, an EMT (epithelial-mesenchymal transition) inducer. Additionally, DEC1 overexpression positively related to the expression of a lymphatic vessel marker podoplanin, but DEC2 exhibited an opposite effect.

Research Products

• [Journal Article] Basic helix-loop-helix transcription factor DEC2 functions as an anti-apoptotic factor during paclitaxel-induced apoptosis in human prostate cancer cells. (2016)
  • Author(s): Liu Q, Wu Y, Yoshizawa T, Yan X, Morohashi S, Seino H, Kato Y, Kijima H.
  • Journal Title: Int J Mol Med Volume: 38 Issue: 6 Pages: 1727-1733
  • DOI: 10.3892/ijmm.2016.2798
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Myofibroblast distribution is associated with invasive growth types of colorectal cancer. (2016)
  • Author(s): Takatsuna M, Morohashi S, Yoshizawa T, Hirai H, Haga T, Ota R, Saito K, Wu Y, Seino H, Aoyagi Y, Terai S, Kijima H.
  • Journal Title: Oncol Rep Volume: 36 Issue: 6 Pages: 3154-3160
  • DOI: 10.3892/or.2016.5202
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Myofibroblasts of the muscle layer stimulate the malignant potential of colorectal cancer. (2016)
  • Author(s): Takatsuna M, Morohashi S, Yoshizawa T, Hirai H, Haga T, Ota R, Wu Y, Morohashi H, Hakamada K, Terai S, Kijima H.
  • Journal Title: Oncol Rep Volume: 36 Issue: 3 Pages: 1251-1257
  • DOI: 10.3892/or.2016.4932
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] <b>Clinicopathological significance of gastric poorly differentiated medullary car</b><b>cinoma </b> (2016)
  • Author(s): Hirai H, Yoshizawa T, Morohashi S, Haga T, Wu Y, Ota R, Takatsuna M, Akasaka H, Hakamada K, Kijima H.
  • Journal Title: Biomedical Research Volume: 37 Issue: 2 Pages: 77-84
  • DOI: 10.2220/biomedres.37.77
  • NAID: 130005147429
  • ISSN: 0388-6107, 1880-313X
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Podoplanin-mediated TGF-β-induced epithelial-mesenchymal transition and its correlation with bHLH transcription factor DEC in TE-11 cells. (2016)
  • Author(s): Wu Y, Liu Q, Yan X, Kato Y, Tanaka M, Inokuchi S, Yoshizawa T, Morohashi S, Kijima H.
  • Journal Title: Int J Oncol. Volume: 48 Issue: 6 Pages: 2310-2320
  • DOI: 10.3892/ijo.2016.3445
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Hypoxia is important in F18 FDG accumulation in thecoma fibroma tumors on F18 FDG PET/CT scans. (2016)
  • Author(s): Seino H, Ono S, Miura H, Morohashi S, Wu Y, Tsushima F, Takai Y, Kijima H.
  • Journal Title: Mol Med Rep. Volume: 13 Issue: 5 Pages: 3821-3827
  • DOI: 10.3892/mmr.2016.5016
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A new histological therapeutic classification system to predict eradicated and residual lymph nodes in breast cancer after neoadjuvant chemotherapy. (2016)
  • Author(s): Morohashi S, Yoshizawa T, Seino H, Hirai H, Haga T, Ota R, Wu Y, Yoshida E, Hakamada K, Kijima H.
  • Journal Title: Oncol Rep. Volume: 35 Issue: 5 Pages: 3592-3598
  • DOI: 10.3892/or.2016.4635
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MORPHOLOGICAL ANALYSIS OF THE RESIDUAL RECTAL MUCOSA IN 12 POSTOPERATIVE ULCERATIVE COLITIS PATIENTS (2016)
  • Author(s): Morohashi S, Morohashi H, Yoshizawa T, Tanaka M, Mikami T, Kagiya T, Saito T, Hirai H, Haga T, Wu Y, Hakamada K, Kijima H.
  • Journal Title: Hirosaki Med. J. Volume: 67 Pages: 92-101
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Phenotypic Characterization of Early Biliary Tract Carcinomas Proposes Two Carcinogenesis Pathways. (2016)
  • Author(s): Haga T, Yoshizawa T, Morohashi S, Hirai H, Saito K, Ota R, Takatusna M, Wu Y, Fukuda S, Kijima H.
  • Journal Title: Hirosaki Med. J. Volume: 67 Pages: 28-38
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Molecular pathology and carcinogenesis of biliary cancer (2015)
  • Author(s): Kijima H, Haga T, Wu Y, Seino H, Hakamada K.
  • Journal Title: Nihon Rinsho Volume: Suppl 3 Pages: 449-156
  • Peer Reviewed
• [Journal Article] 診断に苦慮した乳輪部に発生した巨大尖圭コンジローマの1例 (2015)
  • Author(s): 諸橋 聡子, 吉澤 忠司, 平井 秀明, 羽賀 敏博, 清野 浩子, 呉 雲燕, 泉 美貴, 鬼島 宏
  • Journal Title: 診断病理 Volume: 32 Pages: 159-163
  • Peer Reviewed
• [Journal Article] 【進展度に応じた胆嚢癌の治療戦略】 進行度から見た胆嚢癌の病理学的特徴 (2015)
  • Author(s): 鬼島 宏, 吉澤 忠司, 羽賀 敏博, 平井 秀明, 桜庭 伸吾, 岡野 健介, 高綱 将史, 清野 浩子, 呉 雲燕, 諸橋 聡子
  • Journal Title: 胆と膵 Volume: 36 Pages: 19-23
  • Peer Reviewed
• [Journal Article] <b>Basic helix-loop-helix transcription factor DEC1 regulates the cisplatin-induced apoptotic pathway of human esophageal cancer </b><b>cells </b> (2015)
  • Author(s): Seino H
  • Journal Title: Biomedical Research Volume: 36 Issue: 2 Pages: 89-96
  • DOI: 10.2220/biomedres.36.89
  • NAID: 130005065284
  • ISSN: 0388-6107, 1880-313X
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Involvement of c-Myc in the proliferation of MCF-7 human breast cancer cells induced by bHLH transcription factor DEC2. (2015)
  • Author(s): Wu Y
  • Journal Title: Int J Mol Med. Volume: 35 Issue: 3 Pages: 815-20
  • DOI: 10.3892/ijmm.2014.2042
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Invasive micropapillary carcinoma of the extrahepatic bile duct and its malignant potential. (2014)
  • Author(s): Yoshizawa T, Toyoki Y, Hirai H, Haga T, Toba T, Sakuraba S, Okano K, Wu Y, Seino H, Morohashi S, Hakamada K, Kijima H.
  • Journal Title: Oncology Reports Volume: 32 Issue: 4 Pages: 1355-61
  • DOI: 10.3892/or.2014.3394
  • Peer Reviewed / Open Access
• [Journal Article] Pathological characteristics of early to advanced gallbladder carcinoma and extrahepatic cholangiocarcinoma. (2014)
  • Author(s): Kijima H, Wu Y, Yosizawa T, Suzuki T, Tsugeno Y, Haga T, Seino H, Morohashi S, Hakamada K.
  • Journal Title: J Hepatobiliary Pancreat Sci. Volume: 21 Issue: 7 Pages: 453-8
  • DOI: 10.1002/jhbp.72
  • Peer Reviewed / Open Access
• [Journal Article] Incidental prostate 18F-FDG uptake without calcification indicates the possibility of prostate cancer. (2014)
  • Author(s): Seino H, Ono S, Miura H, Morohashi S, Wu Y, Tsushima F, Takai Y, Kijima H.
  • Journal Title: Oncol Rep. Volume: 31 Issue: 4 Pages: 1517-1522
  • DOI: 10.3892/or.2014.3011
  • Peer Reviewed / Open Access
• [Presentation] TGF-β-induced podoplanin expression is associated with EMT of human esophageal carcinoma TE-11 cells. (2016)
  • Author(s): Wu Y, Liu Q, Yan X, Kato Y, Seino H, Morohashi S, Kijima H.
  • Organizer: 第75回日本癌学会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-10-06
• [Presentation] TGF-β induced epithelial-mesenchymal transition via podoplanin in human esophageal carcinoma TE-11 cells. (2016)
  • Author(s): Wu Y, Liu Q, Yan X, Kato Y, Seino H, Morohashi S, Kijima H.
  • Organizer: 第13回日本病理学会カンファレンス
  • Place of Presentation: 六甲山ホテル（兵庫県・神戸市）
  • Year and Date: 2016-07-29
• [Presentation] Podoplanin-mediated TGF-β-induced EMT and its correlation with bHLH transcription factor DEC in TE-11 cells. (2016)
  • Author(s): Wu Y, Liu Q, Yan X, Kato Y, Yoshizawa T, Seino H, Morohashi S, Kijima H.
  • Organizer: 第105回日本病理学会
  • Place of Presentation: 仙台国際センター（宮城県・仙台市）
  • Year and Date: 2016-05-12
• [Presentation] DEC1 induced by E2-ERα signaling promotes the EMT process of breast cancer cells (2015)
  • Author(s): Yunyan Wu, Qiang Liu, Hideaki Hirai, Tadashi Yoshizawa, Satoko Morohashi, Yukio Kato, Hiroshi Kijima
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場 （愛知県・名古屋市）
  • Year and Date: 2015-05-01
• [Presentation] Involvement of c-Myc in DEC2-induced cell proliferation of breast cancer MCF-7 cells. (2014)
  • Author(s): Yunyan Wu, Hidenobu Sato, Keishu Murakami, Hideaki Hirai, Tadashi Yoshizawa, Hiroko Seino, Satoko Morohashi, Yukio Kato, Hiroshi Kijima
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島国際会場
  • Year and Date: 2014-04-26