1999 年度実績報告書

ヒト癌の発生、進展に関与する遺伝子異常の解析

研究課題

研究課題/領域番号	07272204
研究機関	東北大学
研究代表者	堀井明東北大学, 大学院・医学系研究科, 教授 (40249983)
キーワード	癌抑制遺伝子 / 膵癌 / 子宮内膜癌 / 肺癌 / 腎癌 / 神経芽細胞腫 / DMBT1遺伝子 / PTEN遺伝子
研究概要	1.膵癌において高頻度欠失の見られる領域のうち3箇所(12q,17q,18q)の染色体欠失が予後不良と相関することを明らかにした。また,膵の発癌過程で初期変化と考えられる18qにおいて,同領域のSMAD4遺伝子がホモ欠失している膵癌株に正常遺伝子を導入しても増殖能は抑制されなかった。一つの遺伝子異常が初期変化にあり,かつ予後不良因子である可能性も否定できないが,上記結果を考え合わせると,18qにはSMAD4以外にもがん抑制遺伝子が局在する可能性がある。 2.子宮内癌では,高頻度に遺伝子異常があるPTEN遺伝子を用いた遺伝子治療を試みた。in vitroでは腫瘍細胞の増殖を抑制できたが,ヌードマウス移植癌では腫瘍縮小効果が見られず,実用化には更なる検討を要するものと考えられた。 3.非小細胞肺癌では,10qの高頻度欠失と同領域のDMBT1の異常が癌発生・進展過程で重要な働きをしている高い可能性を見いだした。 4.神経芽細胞腫では14qの高頻度欠失領域の同定,1p32の高頻度欠失と同領域の相互転座点の同定を行った。

研究成果
(20件)

すべてその他

すべて文献書誌 (20件)

[文献書誌] Yatsuoka, T.: "Association of prognosis with loss of 12q, 17p, and 18q, and concordant loss of 6q/17p and 12q/18q in human pancrestic ductal adenocarcinoma"Am. J. Gastroent.. ( in press ). (2000)
[文献書誌] Semba, S.: "Analysis of the candidate target genes for mutation in microsatellite instability-positive cancers of the colorectum, stomach, and endometrium"Int. J. Oncol.. ( in press ). (2000)
[文献書誌] Ikeda, T.: "Anticorresponding mutation of the KRAS and PTEN genes in human endometrial acncer"Oncol. Rep.. ( in press ). (2000)
[文献書誌] Saito, A.: "p24/ING1-ALT1 and p47/ING1-ALT2, distinct alternative transcripts of p33/ING1"J. Hum. Genet.. ( in press ). (2000)
[文献書誌] Kadota, M.: "Identification of a 7-cM region of frequent allelic loss on chromosome band 16p13.3 that is specifically associated with anaplastic thyroid carcinoma"Oncol. Rep.. ( in press ). (2000)
[文献書誌] Ikeda, T.: "Mutational analysis of the CTNNB1 (β-catenin) gene in human endometrial cancer. Frequent mutations at codon 34 that cause nuclear accumulation"Oncol. Rep. 7. 323-326 (2000)
[文献書誌] Hoshi, M.: "Detailed deletion mapping of chromosome band 14q32 in human neuroblasroma defines a 0.5-Mb region of common allelic loss"Br. J. Cancer. ( in press ). (2000)
[文献書誌] Yamato, T.: "Isolation and characterization of the novel gene, TU3A, in a commonly deleted region on 3p14.2-p14.3 in renal cell carcinoma"Cytogenet. Cell Genet.. 87. 291-295 (1999)
[文献書誌] Sakuraba, A.: "Adenovirus-mediated delivery of PTEN gene inhibits cell growth by induction of apoptosis in endometrial cancer"Int. J. Oncol. 15. 1069-1074 (1999)
[文献書誌] Shinoura, T.: "Adenovirus-mediated transfer of p33^<ING> with p53 drastically augments apoptosis in gliomas"Cancer Res.. 59. 5521-5528 (1999)
[文献書誌] Furukawa, T.: "Cloning and characterizstion of human UDP-N-acetylglucosamine : α-1,3-D-mannoside β-1,4-N-acetylglucosaminyltransferase IV-homologue(hGnT-IV-H)gene"J. Hum. Genet.. 44. 397-401 (1999)
[文献書誌] Takeshita, H.: "Expression of the DMBT1 gene is frequently suppressed in human lung cancer"Jpn. J. Cancer Res.. 90. 903-908 (1999)
[文献書誌] Amari, M.: "LOH analyses of premalignant and malignant lesion of the human breast : Frequent LOHs in 8p, 16q, and 17q in atypical ductal hyperplasia"Oncol. Rep.. 6. 1277-1280 (1999)
[文献書誌] Suzuki, A.: "Identification of a 5-cM region of common allelic loss on 8p12-p21 in human breast cancer and genomic analysis of the hEXT1L/EXTR1/EXTL3 gene in this locus"Int. J. Oncol.. 15. 443-451 (1999)
[文献書誌] Komoike, Y.: "Comparative genomic hybridization defines frequent loss on 16q in human anaplastic thyroid carcinoma"Int. J. Oncol.. 14. 1157-1162 (1999)
[文献書誌] Kondo, E.: "The human PMS2L proteins do not interact with hMLH1, a maior DNA mismatch repair protein"J. Biochem.. 125. 818-825 (1999)
[文献書誌] Yatsuoka, T.: "Genomic analysis of the thymine-DNA glycosylase (TDG) gene on 12q22-q24.1 in human pancereatic ductal adenocarcinoma"Int. J. Panc.. 25. 97-102 (1999)
[文献書誌] Han, S.: "Infrequent somatic mutations of the p73 gene in various human cancers"Eur. J. Surg. Oncol.. 25. 194-198 (1999)
[文献書誌] Abe, T.: "Identification of three commonly deleted regions on chromosome arm 6q in human pancreatic cancer"Genes Chromosomes Cancer. 25. 60-64 (1999)
[文献書誌] Mori, Y.: "Chromosome band 16q24 is frequently deleted in human gastric cancer"Br. J. Cancer. 80. 556-562 (1999)

1999 年度 実績報告書

ヒト癌の発生、進展に関与する遺伝子異常の解析

研究代表者

堀井 明 東北大学, 大学院・医学系研究科, 教授 (40249983)

研究成果

[文献書誌] Yatsuoka, T.: "Association of prognosis with loss of 12q, 17p, and 18q, and concordant loss of 6q/17p and 12q/18q in human pancrestic ductal adenocarcinoma"Am. J. Gastroent.. ( in press ). (2000)

[文献書誌] Semba, S.: "Analysis of the candidate target genes for mutation in microsatellite instability-positive cancers of the colorectum, stomach, and endometrium"Int. J. Oncol.. ( in press ). (2000)

[文献書誌] Ikeda, T.: "Anticorresponding mutation of the KRAS and PTEN genes in human endometrial acncer"Oncol. Rep.. ( in press ). (2000)

[文献書誌] Saito, A.: "p24/ING1-ALT1 and p47/ING1-ALT2, distinct alternative transcripts of p33/ING1"J. Hum. Genet.. ( in press ). (2000)

[文献書誌] Kadota, M.: "Identification of a 7-cM region of frequent allelic loss on chromosome band 16p13.3 that is specifically associated with anaplastic thyroid carcinoma"Oncol. Rep.. ( in press ). (2000)

[文献書誌] Ikeda, T.: "Mutational analysis of the CTNNB1 (β-catenin) gene in human endometrial cancer. Frequent mutations at codon 34 that cause nuclear accumulation"Oncol. Rep. 7. 323-326 (2000)

[文献書誌] Hoshi, M.: "Detailed deletion mapping of chromosome band 14q32 in human neuroblasroma defines a 0.5-Mb region of common allelic loss"Br. J. Cancer. ( in press ). (2000)

[文献書誌] Yamato, T.: "Isolation and characterization of the novel gene, TU3A, in a commonly deleted region on 3p14.2-p14.3 in renal cell carcinoma"Cytogenet. Cell Genet.. 87. 291-295 (1999)

[文献書誌] Sakuraba, A.: "Adenovirus-mediated delivery of PTEN gene inhibits cell growth by induction of apoptosis in endometrial cancer"Int. J. Oncol. 15. 1069-1074 (1999)

[文献書誌] Shinoura, T.: "Adenovirus-mediated transfer of p33^<ING> with p53 drastically augments apoptosis in gliomas"Cancer Res.. 59. 5521-5528 (1999)

[文献書誌] Furukawa, T.: "Cloning and characterizstion of human UDP-N-acetylglucosamine : α-1,3-D-mannoside β-1,4-N-acetylglucosaminyltransferase IV-homologue(hGnT-IV-H)gene"J. Hum. Genet.. 44. 397-401 (1999)

[文献書誌] Takeshita, H.: "Expression of the DMBT1 gene is frequently suppressed in human lung cancer"Jpn. J. Cancer Res.. 90. 903-908 (1999)

[文献書誌] Amari, M.: "LOH analyses of premalignant and malignant lesion of the human breast : Frequent LOHs in 8p, 16q, and 17q in atypical ductal hyperplasia"Oncol. Rep.. 6. 1277-1280 (1999)

[文献書誌] Suzuki, A.: "Identification of a 5-cM region of common allelic loss on 8p12-p21 in human breast cancer and genomic analysis of the hEXT1L/EXTR1/EXTL3 gene in this locus"Int. J. Oncol.. 15. 443-451 (1999)

[文献書誌] Komoike, Y.: "Comparative genomic hybridization defines frequent loss on 16q in human anaplastic thyroid carcinoma"Int. J. Oncol.. 14. 1157-1162 (1999)

[文献書誌] Kondo, E.: "The human PMS2L proteins do not interact with hMLH1, a maior DNA mismatch repair protein"J. Biochem.. 125. 818-825 (1999)

[文献書誌] Yatsuoka, T.: "Genomic analysis of the thymine-DNA glycosylase (TDG) gene on 12q22-q24.1 in human pancereatic ductal adenocarcinoma"Int. J. Panc.. 25. 97-102 (1999)

[文献書誌] Han, S.: "Infrequent somatic mutations of the p73 gene in various human cancers"Eur. J. Surg. Oncol.. 25. 194-198 (1999)

[文献書誌] Abe, T.: "Identification of three commonly deleted regions on chromosome arm 6q in human pancreatic cancer"Genes Chromosomes Cancer. 25. 60-64 (1999)

[文献書誌] Mori, Y.: "Chromosome band 16q24 is frequently deleted in human gastric cancer"Br. J. Cancer. 80. 556-562 (1999)

1999 年度実績報告書

堀井明東北大学, 大学院・医学系研究科, 教授 (40249983)