Conversion of Terminally Differentiated Cells to Progenitor Cells-A Trial of Tissue Regeneration Not by Targeting Stem Cells

2011 Fiscal Year Final Research Report

• Project/Area Number: 21659454
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Dental engineering/Regenerative dentistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: IKEDA Masaaki 東京医科歯科大学, 大学院・医歯学総合研究科, 准教授 (20193211)
• Project Period (FY): 2009 – 2011
• Keywords: 再生歯学

Research Abstract

The pathways regulated by p53 and RB tumor suppressors play important roles in differentiation and irreversible cell-cycle arrest in terminally differentiated cells. To induce dedifferentiation and proliferation of terminally differentiated cells, we investigated functional roles of DRIL1 and its closely related DRIL2, family members of ARID(AT-rich interaction domain) DNA-binding proteins, in these major tumor suppressor pathways. We found that DRIL1 cooperates with p53 to activate pro-arrest p21^WAF1 transcription, and that DRIL1 and DRIL2 play important roles in E2F-target gene expression and cell cycle progression, and that DRIL2 function is required for osteogenic differentiation. In addition, our results suggest that, in addition to DRIL1 or DRIL2 knockdown, inhibition of p53 and RB functions is required for inducing dedifferentiation and proliferation of terminally differentiated cells. These results provide important insights to the conversion of terminally differentiated cells into progenitor cells.

Research Products

• [Journal Article] Cooperation between ARID3A and p53 in the transcriptional activation of p21WAF1 in response to DNA damage (2012)
  • Author(s): Lestari W, Ichwan SJA, Otsu M, Yamada S, Iseki S, Shimizu S, Ikeda MA
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 417 Pages: 710-716
• [Journal Article] Inability of p53-Reactivating compounds Nutlin-3 and RITA to overcome p53 resistance in tumor cells deficient for p53Ser46 phosphorylation (2012)
  • Author(s): Ma, T, Yamada S, Ichwan SJA, Ohtani K, Iseki S, Otsu M, Ikeda MA
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 417 Pages: 931-937
• [Journal Article] Cytotoxic effect of chitosan against oral cancer cell lines is molecular-weight-dependent and cell-type-specific (2012)
  • Author(s): Wimardhani SY, Sunia DF, Freisleben H-J, Septelia Wanandi SI, Ikeda MA
  • Journal Title: Int. J. Oral Res Volume: 3
• [Journal Article] Essential Role of Caspase-8 in p53/p73-Dependent Apoptosis Induced by Etoposide in Head and Neck Carcinoma Cells (2011)
  • Author(s): Liu J, Uematsu H, Tsuchida N, Ikeda MA
  • Journal Title: Molecular Cancer Volume: 10 Pages: 95
• [Journal Article] Expression of cyclin E in postmitotic neurons during development and in the adult mouse brain (2011)
  • Author(s): Ikeda Y, Matsunaga Y, Takiguchi M, Ikeda MA
  • Journal Title: Gene Expr Patterns Volume: 11 Pages: 64-71
• [Journal Article] Coactivation of SF-1-mediated transcription of steroidogenic enzymes by Ubc9 and PIAS1 (2011)
  • Author(s): Suda N, Shibata H, Kurihara I, Ikeda Y, Kobayashi S, Yokota K, Murai-Takeda A, Nakagawa K, Oya M, Murai M, Rainey WE, Saruta T, Itoh H.
  • Journal Title: Endocrinology Volume: 152 Pages: 2266-2277
• [Journal Article] Hoxb4 transduction down-regulates Geminin protein, providing hematopoietic stem and progenitor cells with proliferation potential (2010)
  • Author(s): Ohno Y, Yasunaga S, Ohtsubo M, Mori S, Tsumura M, Okada S, Ohta T, Ohtani K, Kobayashi M, Takihara Y
  • Journal Title: Proc Natl Acad Sci USA Volume: 107 Pages: 21529-21534
• [Journal Article] Association of Caspase-8 Mutation with Chemoresistance to Cisplatin in HOC313 Head and Neck Squamous Cell Carcinoma Cells (2009)
  • Author(s): Liu J, Uematsu H, Tsuchida N, Ikeda MA
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 390 Pages: 989-994
• [Journal Article] Detection of two novel mutations and relatively high incidence of H-RAS mutations in Vietnamese oral cancer (2009)
  • Author(s): Murugan AK, Hong NT, Cue TTK, Hung NC, Munirajan AK, Ikeda MA, Tsuchida N
  • Journal Title: Oral Oncology Volume: 45 Pages: e161-166
• [Journal Article] E2F-like elements in p27(Kip1) promoter specifically sense deregulated E2F activity (2009)
  • Author(s): Ozono E, Komori H, Iwanaga R, Ikeda MA, Iseki S, Ohtani K
  • Journal Title: Genes Cells Volume: 14 Pages: 89-99
• [Journal Article] In Vitro Antioxidant and Antiproliferative Activities of Three Malaysian Sea Cucumber Species (2009)
  • Author(s): Althunibat OY, Hashim, RB, Taher M, Daud JM, Ikeda MA, Zali BI
  • Journal Title: European Journal of Scientific Research Volume: 37 Pages: 376-387
• [Journal Article] NE5A1 is required for functional maturation of Sertoli cells during postnatal development
  • Author(s): Kato T, Esaki M, Matsuzawa A, Ikeda Y
  • Journal Title: Reproduction Volume: (in press)
• [Presentation] Inability of p53-Reactivating compounds Nutlin-3 and RITA to overcome p53 resistance in tumor cells deficient for p53Ser46 phosphorylation (2012)
  • Author(s): Teng Ma Shumpei Yamada, Solachuddin J. A. Ichwan, Sachiko Iseki, Kiyoshi Ohtani, Megumi Otsu, Masa-Aki Ikeda
  • Organizer: 3rd Cancer Targets and Therapeutics
  • Place of Presentation: Las Vegas, Nevada, USA
  • Year and Date: 20120227-28
• [Presentation] Role of ARID3A and ARID3B in Cell Growth and E2F-target gene expression (2012)
  • Author(s): Khandakar A S M Saadat, Endrawan Pratama, Kiyoshi Ohtani, Masa-Aki Ikeda
  • Organizer: 2nd Heidelberg Forum for Young Life Scientist
  • Place of Presentation: Heidelberg, Germany
  • Year and Date: 20120223-24
• [Presentation] Inability of p53-Reactivating compounds Nutlin-3 and RITA to overcome p53 resistance in tumor cells deficient for p53Ser46 phosphorylation (2012)
  • Author(s): Teng Ma Shumpei Yamada, Solachuddin J. A. Ichwan, Sachiko Iseki, Kiyoshi Ohtani, Megumi Otsu, Masa-Aki Ikeda
  • Organizer: 2nd Heidelberg Forum for Young Life Scientists
  • Place of Presentation: Heidelberg, Germany
  • Year and Date: 20120223-24
• [Presentation] 生殖腺特異的SF-1ノックアウトマウスの精巣におけるセルトリ細胞の分化異常 (2012)
  • Author(s): 池田やよい、加藤朋子
  • Organizer: 第117回日本解剖学会総会・全国学術集会
  • Place of Presentation: 甲府
  • Year and Date: 20120000
• [Presentation] Low Molecular Weight Chitosan : Mechanism of Antitumor Activity against Oral Cancer Cells (2011)
  • Author(s): Yuniardini Septorini Wimardhani, Dewi Fatma Suniarti, HJ Freisleben, Septelia Inawati Wanandi, Masa-Aki Ikeda
  • Organizer: FDI-IDA Joint Meeting
  • Place of Presentation: Semarang, Indonesia
  • Year and Date: 20111112-13
• [Presentation] Low Molecular Weight Chitosan : Antitumor Efficiency against Oral Cancer Cells (2011)
  • Author(s): Yuniardini Septorini Wimardhani, Dewi Fatma Suniarti, HJ Freisleben, Septelia Inawati Wanandi, Masa-Aki Ikeda
  • Organizer: The 25th International Association for Dental Research South East Asian Regional Meeting
  • Place of Presentation: Singapore
  • Year and Date: 20111028-30
• [Presentation] Postnatal development of the gonad specific SF-1 KO mouse testis (2011)
  • Author(s): Ikeda Y, Kato T
  • Organizer: The Endocrine Society's 93rd Annual Meeting
  • Place of Presentation: Boston
  • Year and Date: 20110000
• [Presentation] 生殖腺特異的SF-1ノックアウトマウスにおける生殖腺の組織学的解析 (2011)
  • Author(s): 加藤朋子,池田やよい
  • Organizer: 第84回日本内分泌学会学術総会
  • Place of Presentation: 神戸
  • Year and Date: 20110000
• [Presentation] Inability of Nutlin-3 and RITA to overcome p53 resistance in tumor cells deficient for p53Ser46 phosphorylation (2011)
  • Author(s): Teng Ma, Shumpei Yamada, Solachuddin J. A Ichiwan, Kiyoshi Ohtani, Megumi Ostu, Masa-Aki Ikeda
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-16
• [Presentation] Role of ARID3A and ARID3B in Cell Growth and E2F-Target Gene Expression (2011)
  • Author(s): Khandakar A S M Saadat, Endrawan Pratama, Kiyoshi Ohtani, Masa-Aki Ikeda
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-16
• [Presentation] Role of ARID3A in p53-mediated Transcriptional Transactivation of p21WafI/CipI (2011)
  • Author(s): Widya Lestari, Solachuddin J. A Ichwan, Megumi Otsu, Shumpei Yamada, Shihoko Shimizu, Masa-Aki Ikeda
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-14
• [Presentation] Inhibition of two chitosans with different molecular weight against the growth of several oral cancer cell lines (2011)
  • Author(s): Yuniardini Septorini Wimardhani, Dewi Fatma Suniarti, Hans-Joachim Freisleben, Septelia Inawati Wanandi, Masa-Aki Ikeda
  • Organizer: Congress of Indonesian Dental Association
  • Place of Presentation: Bali, Indonesia
  • Year and Date: 2011-04-01
• [Presentation] Effect of Nutlin-3 on p53 resistance in tumor cells lacking the ability to phosphorylate Ser46 on p53 (2010)
  • Author(s): Teng Ma, Shumpei Yamada, Ichwan Solachuddin J. A., Megumi Ostu, Kiyoshi Ohtani, Masa-Aki Ikeda
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同年会
  • Place of Presentation: 神戸
  • Year and Date: 20101207-10
• [Presentation] Caspase-8 and p53/p73 deficiencies confer resistance to drug induced apoptosis in head and Neck carcinoma cells (2010)
  • Author(s): Juan Liu, Nobuo Tsuchida, Masa-Aki Ikeda
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 20100922-24
• [Presentation] In vitro inhibition of growth and induction of apoptosis in human oral cancer cell lines by thymoquinone (2010)
  • Author(s): Ichwan Solachuddin J. A., Masa-Aki Ikeda
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 20100922-24
• [Presentation] Cyclin E expression in early neural stem cells during adult hippocampal neurogenesis (2010)
  • Author(s): Yayoi Ikeda, Masahiko Takiguchi, Masa-Aki Ikeda
  • Organizer: Keystone Symposia "Stem Cell Differentiation and Dedifferentiation"
  • Place of Presentation: Keystone, Colorado, USA.
  • Year and Date: 20100215-20
• [Presentation] Cyclin E expression in early neural stem cells during adult hippocampal neurogenesis Keystone Symposia : Stem Cell Differentiation and Dedifferentiation (2010)
  • Author(s): Ikeda Y, Takiguchi M, Ikeda M-A
  • Year and Date: 20100000
• [Presentation] Effects of gestational diethylstilbestrol treatment on gonadal differentiation (2010)
  • Author(s): Ikeda Y, Kato T, Takiguchi M
  • Organizer: 14th International Congress of Endocrinology
  • Place of Presentation: Kyoto
  • Year and Date: 20100000
• [Presentation] Effects of voluntary physical activity on cyclin E expression in the subgranular layer of the mouse hippocampal dentate gyrus (2010)
  • Author(s): Ikeda Y, Takiguchi M, Ikeda M-A
  • Organizer: Neuroscience 2010(40th Annual Meeting)
  • Place of Presentation: San Diego
  • Year and Date: 20100000
• [Presentation] マウス海馬歯状回顆粒下層における細胞増殖因子サイクリンEの発現 (2010)
  • Author(s): 池田やよい,滝口雅人,松永裕子,池田正明
  • Organizer: Neuro2010(第33回日本神経科学大会/第53回日本神経化学会大会/第20回日本神回路学会大会合同大会)
  • Place of Presentation: 神戸
  • Year and Date: 20100000
• [Presentation] Expression of cyclin E in the cerebral and cerebellar cortices, Anti-cancer properties of and Thymoquinone, constituents of Nigella sativa, on oral cancer cell lines (2009)
  • Author(s): Ikeda Y, Matsunaga Y, Ikeda M-A, Ichwan Solachuddin J. A., Muhammad Taher, Widya Lestari, M. Termidzi Junaidi, Masa-Aki Ikeda
  • Organizer: 第32回日本神経科学大会,第32回日本分子生物学会年会
  • Place of Presentation: 名古屋,横浜
  • Year and Date: 20091209-12
• [Presentation] Drug-specific Effects of Caspase-8 and p53/p73 Alterations on Chemosensitivity in Head and Neck Carcinoma Cells (2009)
  • Author(s): Juan Liu, Nobuo Tsuchida, Masa-Aki Ikeda
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 20091209-12
• [Presentation] Spatiotemporal analysis of Cdk2 interraction with its regulatory proteins (2009)
  • Author(s): Philippe Olivier D. L., Masa-Aki Ikeda
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 20091209-12
• [Presentation] Effect of Nutlin-3 on p53 resistance in tumor cells lacking the ability to phosphorylate Ser46 on p53 (2009)
  • Author(s): Teng Ma, Shumpei Yamada, Ichwan Solachuddin J. A., Megumi Ostu, Kiyoshi Ohtani, Masa-Aki Ikeda
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 20091209-12
• [Presentation] 生殖腺発生に働く転写調節因子へのエストロゲン暴露の影響 (2009)
  • Author(s): 池田やよい
  • Organizer: 第82回日本内分泌学会学術総会
  • Place of Presentation: 群馬
  • Year and Date: 20090000
• [Presentation] 卵胞細胞特異的SF-1ノックアウトマウスの卵巣分化 (2009)
  • Author(s): 池田やよい
  • Organizer: 第82回日本内分泌学会総会
  • Place of Presentation: 群馬
  • Year and Date: 20090000
• [Presentation] 胎生期DES暴露による生殖腺発生初期への影響 (2009)
  • Author(s): 池田やよい
  • Organizer: 第19回懇話会・シンポジウ
  • Place of Presentation: 日本解剖学会関東支部
  • Year and Date: 20090000
• [Presentation] Abnormal ovarian development by granulosa cell-specific ablation of the orphan nuclear receptor steroidogenic factor 1 (2009)
  • Author(s): Ikeda Y, Pelusi C, Parker KL
  • Organizer: XXXVI International Congress of Physiological Sciences
  • Place of Presentation: Kyoto
  • Year and Date: 20090000
• [Book] Therapeutic Targeting of p53-Mediated Apoptosis Pathway in Head and Neck Squamous Cell Carcinomas : Current Progress and Challenges, Tumor Suppressor Genes (2012)
  • Author(s): Ichwan SJA, Bakhtiar MT, Ohtani K, Ikeda MA
  • Total Pages: 129-144
  • Publisher: InTech
• [Book] Hormones and cerebellar development in The Handbook of the Cerebellum and Cerebellar Disorders
  • Author(s): Koibuchi1 N, Ikeda Y
  • Publisher: Springer(in press)