Dysregulation of hedgehog signaling and tumorigenesis

• Project/Area Number: 23501269
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Kitasato University
• Principal Investigator: MIYASHITA Toshiyuki 北里大学, 医学部, 教授 (60174182)
• Co-Investigator(Renkei-kenkyūsha): KAMEYAMA Kohzoh 北里大学, 医学部, 講師 (40214556) ; NAGAO Kazuaki 北里大学, 医学部, 助教 (60392487)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 母斑基底細胞癌症候群 / PTCH1 / 癌抑制遺伝子 / 歯原性腫瘍

Research Abstract

In order to investigate the molecular mechanism of tumor formation in NBCCS patients, we analyzed gene mutations in 10 cases of KCOT, 2 cases of meningioma and 1 case each of medulloblastoma and ovarian leiomyoma. As a result, 1 sample each of meningioma, medulloblastoma and ovarian leiomyoma had a pathogenic somatic mutation (2nd hit), whereas only one out of ten KCOT samples carried a possible pathogenic mutation.
Therefore, KCOT is suggested to arise through a mechanism distinct from that for other tumors.

Research Products

• [Journal Article] Downregulation of microRNA-431 by human interferon-β inhibits viability of medulloblastoma and glioblastoma cells via upregulation of SOCS6 (2014)
  • Author(s): Tanaka.T., Arai, M., Jiang, X., Sugaya, S., Kanda, T., Fujii, K., Kita, K., Sugita, K., Imazeki, F., Miyashita, T., Kaneda, A., and Yokosuka, O
  • Journal Title: Int. J. Oncol Volume: 44 Issue: 5 Pages: 1685-1690
  • DOI: 10.3892/ijo.2014.2317
  • Peer Reviewed
• [Journal Article] Downregulation of microRNA-431 by human interferon-β inhibits viability of medulloblastoma and glioblastoma cells via upregulation of SOCS6. (2014)
  • Author(s): Tanaka.T., Arai, M., Jiang, X., Sugaya, S., Kanda, T., Fujii, K., Kita, K., Sugita, K., Imazeki, F., Miyashita, T., Kaneda, A., and Yokosuka, O.
  • Journal Title: Int. J. Oncol. Volume: 44 Pages: 1685-1690
  • Peer Reviewed
• [Journal Article] Frameshift mutation in the PTCH2 gene can cause nevoid basal cell carcinoma syndrome (2013)
  • Author(s): Fujii. K., Ohashi, H. ,Suzuki, M., Hatsuse, H., Shiohama, T., Uchikawa, H., and Miyashita, T
  • Journal Title: Fam. Cancer Volume: 12 Pages: 611-614
  • Peer Reviewed
• [Journal Article] Falx cerebri calcification and microphthalmia in Gorlin syndrome (2013)
  • Author(s): Fujita Y., Fujita T., Fujii, K., and Miyashita, T
  • Journal Title: Neurol. Clin. Neurosci Volume: 1 Pages: 88-89
  • Peer Reviewed
• [Journal Article] Molecular pathogenesis of keratocystic odontogenic tumors developing in nevoid basal cell carcinoma syndrome (2013)
  • Author(s): Suzuki, M., Nagao, K., Hatsuse, H., Sasaki, R., Saito, K., Fujii, K., and Miyashita, T
  • Journal Title: Oral Surg. Oral Med. Oral Pathol. Oral Radiol Volume: 116 Pages: 348-353
  • Peer Reviewed
• [Journal Article] Role of FK506 binding protein 5 (FKBP5) in osteoclast differentiation. (2013)
  • Author(s): Kimura, M., Nagai, T., Matsushita. R., Hashimoto. A., Miyashita. T., and Hirohata. S.
  • Journal Title: Mod. Rheumatol. Volume: 23 Pages: 1133-1139
  • DOI: 10.1007/s10165-012-0809-4
  • Peer Reviewed
• [Journal Article] Frameshift mutation in the PTCH2 gene can cause nevoid basal cell carcinoma syndrome. (2013)
  • Author(s): Fujii. K., Ohashi, H. ,Suzuki, M., Hatsuse, H., Shiohama, T., Uchikawa, H., and Miyashita, T.
  • Journal Title: Fam. Cancer Volume: 12 Issue: 4 Pages: 611-614
  • DOI: 10.1007/s10689-013-9623-1
  • Peer Reviewed
• [Journal Article] Falx cerebri calcification and microphthalmia in Gorlin syndrome. (2013)
  • Author(s): Fujita Y., Fujita T., Fujii, K., and Miyashita, T.
  • Journal Title: Neurol. Clin. Neurosci. Volume: 1 Pages: 88-89
  • Peer Reviewed
• [Journal Article] Molecular pathogenesis of keratocystic odontogenic tumors developing in nevoid basal cell carcinoma syndrome. (2013)
  • Author(s): Suzuki, M.,Nagao, K., Hatsuse, H., Sasaki, R., Saito, K., Fujii, K., Miyashita, T.
  • Journal Title: Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Volume: 116 Issue: 3 Pages: 348-353
  • DOI: 10.1016/j.oooo.2013.06.017
  • Peer Reviewed
• [Journal Article] Two cases of nevoid basal cell carcinoma syndrome associated with meningioma caused by a PTCH1 or SUFU germline mutation (2012)
  • Author(s): Kijima C., Miyashita T., Suzuki M., Oka H., and Fujii K
  • Journal Title: Fam. Cancer Volume: 11 Pages: 565-570
  • Peer Reviewed
• [Journal Article] Selective haploinsufficiency of longer isoforms of PTCH1 protein can cause nevoid basal cell carcinoma syndrome (2012)
  • Author(s): Suzuki, M., Hatsuse, H., Nagao, K., Takayama, Y., Kameyama, K., Kabasawa, Y., Omura, K., Yoshida, M., Fujii, K., and Miyashita, T
  • Journal Title: J. Hum. Genet Volume: 57 Pages: 422-426
  • NAID: 10030965596
  • Peer Reviewed
• [Journal Article] Heterozygous Tandem Duplication Within the PTCH1 Gene Results in Nevoid Basal Cell Carcinoma Syndrome (2012)
  • Author(s): Kosaki, R., Nagao, K., Kameyama, K., Suzuki, M., Fujii, K., and Miyashita T
  • Journal Title: Am. J. Med. Genet A Volume: 158A Pages: 1724-1728
  • Peer Reviewed
• [Journal Article] Splicing aberration in nevoid basal cell nevus syndrome (2012)
  • Author(s): Ishitsuka, Y., Furuta, J., Miyashita, T., and Otsuka, F
  • Journal Title: Acta Derm. Venereol Volume: 92 Pages: 619-620
  • Peer Reviewed
• [Journal Article] Nationwide survey of nevoid basal cell carcinoma syndrome in Japan revealing the low frequency of basal cell carcinoma (2012)
  • Author(s): Endo, M., Fujii, K., Sugita, K., Saito, K., Kohno, Y., and Miyashita, T
  • Journal Title: Am. J. Med. Genet A Volume: 158A Pages: 351-357
  • Peer Reviewed
• [Journal Article] Splicing aberration in nevoid basal cell nevus syndrome (2012)
  • Author(s): Ishitsuka, Y., Furuta, J., Miyashita, T.
  • Journal Title: Acta Derm. Venereol. Volume: 92 Issue: 6 Pages: 619-620
  • DOI: 10.2340/00015555-1332
  • Peer Reviewed
• [Journal Article] Heterozygous Tandem Duplication Within the PTCH1 Gene Results in Nevoid Basal Cell Carcinoma Syndrome (2012)
  • Author(s): Kosaki, R., Nagao, K., Kameyama, K., Suzuki, M., Fujii, K., and Miyashita T.
  • Journal Title: Am. J. Med. Genet. A Volume: 158A Issue: 7 Pages: 1724-1728
  • DOI: 10.1002/ajmg.a.35412
  • Peer Reviewed
• [Journal Article] Selective haploinsufficiency of longer isoforms of PTCH1 protein can cause nevoid basal cell carcinoma syndrome (2012)
  • Author(s): Suzuki, M., Hatsuse, H., Nagao, K., Takayama, Y., Kameyama, K., Kabasawa, Y., Omura, K., Yoshida, M., Fujii, K., and Miyashita, T.
  • Journal Title: J. Hum. Genet. Volume: 57 Issue: 7 Pages: 422-426
  • DOI: 10.1038/jhg.2012.45
  • NAID: 10030965596
  • Peer Reviewed
• [Journal Article] RCAN1 is an important mediator of glucocorticoid-induced apoptosis in human leukemic cells (2012)
  • Author(s): Nagao, K., Iwai Y., and Miyashita T.
  • Journal Title: PLOS ONE Volume: 7 Issue: 11 Pages: e49926-e49926
  • DOI: 10.1371/journal.pone.0049926
  • Peer Reviewed
• [Journal Article] Nationwide survey of nevoid basal cell carcinoma syndrome in Japan revealing low frequency of basal cell carcinoma (2012)
  • Author(s): Endo M, Fujii K, Sugita K, Saito K, Kohno Y, Miyashita T
  • Journal Title: Am J Med Genet A Volume: 158A Issue: 2 Pages: 351-7
  • DOI: 10.1002/ajmg.a.34421
  • Peer Reviewed
• [Journal Article] Nationwide survey of nevoid basal cell carcinoma syndrome in Japan revealing the low frequency of basal cell carcinoma (2012)
  • Author(s): Endo, M., Fujii, K., Sugita, K., Saito, K., Kohno, Y., and Miyashita, T.
  • Journal Title: American Journal of Medical Genetics A Volume: 158A Pages: 351-357
  • Peer Reviewed
• [Journal Article] Entire PTCH1 deletion is a common event in point mutation-negative cases with nevoid basal cell carcinoma syndrome in Japan (2011)
  • Author(s): Nagao, K., Fujii, K., Saito, K., Sugita, K., Endo, M., Motojima, T., Hatsuse, H. and Miyashita, T
  • Journal Title: Clin. Genet Volume: 79 Pages: 196-198
  • Peer Reviewed
• [Journal Article] Entire PTCH1 deletion is a common event in point mutation-negative cases with nevoid basal cell carcinoma syndrome in Japan (2011)
  • Author(s): Nagao, K., Fujii, K., Saito, K., Sugita, K., Endo, M., Motojima, T., Hatsuse, H. and Miyashita, T.
  • Journal Title: Clinical Genetics Volume: 79 Issue: 2 Pages: 196-198
  • DOI: 10.1111/j.1399-0004.2010.01527.x
  • Peer Reviewed
• [Journal Article] 見逃してはいけない家族性腫瘍：本邦における母斑基底細胞癌症候群の遺伝子変異と臨床的特徴 (2011)
  • Author(s): 宮下俊之、桐生麻衣子、齋藤加代子、杉田克生、遠藤真美子、藤井克則
  • Journal Title: 家族性腫瘍 Volume: 11 Pages: 14-18
  • NAID: 130007529694
• [Presentation] Functional analysis of a sonic hedgehog signaling pathway inhibitor SUFU (2013)
  • Author(s): 長尾和右、宮下俊之
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 母斑基底細胞癌症候群で見出されたスプライシング変異と異常mRNA の分解 (2012)
  • Author(s): 志村将人、鈴木麻衣子、初瀬洋美、長尾和右、高山吉永、亀山孝三、藤井克則、宮下俊之
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] PTCH2とSUFU 遺伝子に配偶子変異をもつ母斑基底細胞癌症候群の検討 (2012)
  • Author(s): 鈴木麻衣子、長尾和右、高山吉永、岡秀宏、藤井克則、宮下俊之
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] Suppressor of fused (SUFU)遺伝子の配偶子変異は高い髄芽腫の発症リスクをもたらす (2012)
  • Author(s): 鈴木麻衣子、宮下俊之、木島千尋、岡秀宏、藤井清孝
  • Organizer: 第16回日本家族性腫瘍学会学術集会
  • Place of Presentation: 大阪
• [Presentation] PTCH2とSUFU遺伝子に配偶子変異をもつ母斑基底細胞癌症候群の検討 (2012)
  • Author(s): 鈴木麻衣子、長尾和右、高山吉永、岡秀宏、藤井克則、宮下俊之
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] 母斑基底細胞癌症候群で見出されたスプライシング変異と異常mRNAの分解 (2012)
  • Author(s): 志村将人、鈴木麻衣子、初瀬洋美、長尾和右、高山吉永、亀山孝三、藤井克則、宮下俊之
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] Gorlin症候群の遺伝子解析 (2012)
  • Author(s): 宮下俊之
  • Organizer: 厚生労働科学研究費補助金 難治性疾患克服研究事業(招待講演)
  • Place of Presentation: 神戸
• [Presentation] 母斑基底細胞癌症候群の分子遺伝学 (2011)
  • Author(s): 宮下俊之
  • Organizer: 第56回日本人類遺伝学会・第11回東アジア人類遺伝学会共同大会
  • Place of Presentation: 千葉
• [Presentation] 日本における母斑性基底細胞癌症候群における基底細胞癌発症率 (2011)
  • Author(s): 藤井克則、宮下俊之
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 母斑基底細胞癌症候群に発症した歯原性腫瘍の遺伝子解析 (2011)
  • Author(s): 宮下俊之、桐生麻衣子、佐々木亮、齋藤加代子、藤井克則
  • Organizer: 遺伝医学合同学術集会
  • Place of Presentation: 京都
• [Presentation] 母斑基底細胞癌症候群に発症した歯原性腫瘍の遺伝子解析 (2011)
  • Author(s): 宮下俊之、桐生麻衣子、佐々木亮、齋藤加代子、藤井克則
  • Organizer: 家族性腫瘍学会
  • Place of Presentation: 京都
• [Presentation] 母斑基底細胞癌症候群に発症する角化嚢胞性歯原性腫瘍の腫瘍化機序の解析 (2011)
  • Author(s): 鈴木麻衣子、長尾和右、高山吉永、藤井克則、宮下俊之
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 母斑基底細胞癌症候群に発症した角化嚢胞性歯原性腫瘍の発症機序の解析 (2011)
  • Author(s): 鈴木麻衣子、長尾和右、高山吉永、亀山孝三、藤井克則、宮下俊之
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] 母斑基底細胞癌症候群の分子遺伝学 (2011)
  • Author(s): 宮下俊之
  • Organizer: 第56回日本人類遺伝学会(招待講演)
  • Place of Presentation: 千葉
• [Presentation] PTCH1遺伝子以外の遺伝子変異によって発症する母斑基底細胞癌症候群 ―多遺伝子1症候群?―
  • Author(s): 宮下俊之、鈴木麻衣子、長尾和右、初瀬弘美、藤井克則
  • Organizer: 第17回日本家族性腫瘍学会学術集会
  • Place of Presentation: 別府
• [Presentation] グルココルチコイド誘導性アポトーシスの解析
  • Author(s): 岩井祐二郎、高山吉永、亀山孝三、初瀬洋美、長尾和右、宮下俊之
  • Organizer: 第26回北里大学バイオサイエンスフォーラム
  • Place of Presentation: 相模原
• [Presentation] Gorlin症候群におけるPTCH2変異の同定
  • Author(s): 藤井克則、大橋博文、内川英紀、塩浜直、宮下俊之
  • Organizer: 第25回千葉県小児神経懇話会
  • Place of Presentation: 千葉
• [Presentation] CRISPR/Cas9システムを用いたヘッジホッグシグナル伝達系構成遺伝子ノックアウト細胞株の作製
  • Author(s): 長尾和右、遠藤葉月、加藤千勢、初瀬洋美、高山吉永、亀山孝三、宮下俊之
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Book] 希少疾患/難病 の診断・治療と製品開発 (2012)
  • Author(s): 藤井 克則、宮下 俊之
  • Total Pages: 1270
  • Publisher: 技術情報協会
• [Book] Human SOS Biological Science (2012)
  • Author(s): Fujii, K., Suzuki, N., Uchikawa, H., Sugita, K., and Miyashita, T
  • Total Pages: 121
  • Publisher: Transworld Research Network
• [Remarks] ホームページ等
  • URL: http://www.med.kitasato-u.ac.jp/~molgen/
• [Remarks] 北里大学医学部分子遺伝学
  • URL: http://www.med.kitasato-u.ac.jp/~molgen/
• [Remarks] 北里大学分子遺伝
  • URL: http://www.med.kitasato-u.ac.jp/~molgen/index.html
• [Remarks]
  • URL: http://www.med.kitasato-u.ac.jp/~molgen/index.html