1999 Fiscal Year Annual Research Report

ヒト肝発癌におけるG1期制御機構異常の役割に関する研究

Research Project

Project/Area Number	10770607
Research Institution	The University of Tokyo
Principal Investigator	回愛民東京大学, 医学部・附属病院, 助手 (70301108)
Keywords	肝細胞癌 / 細胞周期 / p16^<INK$> / Rb / p21^<WAF1 / CIP1 > / p53 / 転移
Research Abstract	p16^<INK$>とRbは細胞周期G1期を制御する重要な遺伝子である。昨年の研究でわれわれはRb蛋白発現異常(発現欠失と過剰発現)が肝癌の進展、転移を促進するという知見を得られて、今年ひき続き肝癌進展、転移過程におけるp16^<INK$>の発現異常の役割及びRbとの関連性を検討した。P16^<INK$>蛋白欠失は肝癌原発巣と転移巣においてそれぞれ36%と74%と認められ、p16^<INK$>発現異常は転移と相関することが考えられた(P=0.001)。P16^<INK$>蛋白欠失はRb蛋白過剰発現と有意に相関した。P16^<INK$>とRbの発現異常は低分化癌、血管浸潤がある癌において高率に認められた。P16^<INK$>とRbの同時欠失は原発巣と比べて転移巣の方が有意に高率であった(P=0.01)。結論:p16^<INK$>とRbの発現異常は肝癌の進展、転移に促進的に働いている。 p21^<WAF1/CIP1 >はp53依存性またはp53非依存性的に細胞周期調節因子として作用している。p53機能喪失(mutationあるいはoncoproteinと結合)の場合、p53蛋白の半減期が延長し、過剰発現になる。本研究は肝癌におけるp21^<WAF1/CIP1 >とp53蛋白の発現を免疫染色により解析し、p21^<WAF1/CIP1 >蛋白発現とp53機能との関連性を検討した。肝癌65例の81腫瘍において、p53:43/81(53%),p21^<WAF1/CIP1 >:22/81(27%)の陽性率であった。p21^<WAF1/CIP1 >陽性率は、p53陽性群では43例の5例(11.6%)で、p53陰性群では38例の17例(44.7%)であり、後者で有意に高率であった(p<0.001)。p21^<WAF1/CIP1 >発現と臨床病理因子(腫瘍分化度、腫瘍径、肝内転移、脈管侵襲)との相関は認められなかった。p53の発現は、高分化群と比べて低分化群では有意に高率であった(35% vs 80%,p<0.01)。結論:肝癌において、p21^<WAF1/CIP1 >蛋白発現低下は高頻度に認められ,p21^<WAF1/CIP1 >発現は主にp53より誘導される。

Research Products

(12 results)

All Other

All Publications (12 results)

[Publications] 回愛民,他4名: "Over-expression and lack of retinoblastoma protein are associated with turnor progression and metastasis in hepatocellular carcinoma"International Journal of Cancer. 84巻. 604-608 (1999)
[Publications] 回愛民,他5名: "Decreased p27^<kip1> expression and cyclin D1 ovexexpression, alone and in combination, influence recurrence and survival of pationts with"Hepatology. 30巻5号. 1167-1173 (1999)
[Publications] 回愛民,幕内雅敏: "Molecular Basis of Maltistep Hepatocarcinogenesis : Genetic and Epigenetic events"Scandinavian,Journal of Gastroenterology. 8巻. 737-742 (1999)
[Publications] 回愛民,幕内雅敏: "細胞周期からみた肝癌の悪性度予測"外科. 62巻3号. 293-297 (2000)
[Publications] 回愛民,他4名: "Loss of p16^<INK4> protein, alone and together with loss of retinoblastoma protein, correlate with hepatocellular carcinoma progression"Cancer Letters. 発表予定. (2000)
[Publications] 史亜州、回愛民、他4名: "Reduced p21^<WAF1/CIP1> protein expression is predominantly related to altered p53 in hepatocellular carcinomas"British Journal of Cancer. 発表予定. (2000)
[Publications] 回愛民,他5名: "p27^<kip1> expression in normal epithelia, precancerous lesions and carcinomas of the gall- bladder : association with cancer progression"Hepatology. 31巻4号(発表予定). (2000)
[Publications] 回愛民,他6名: "Left hemihepatectomy in living donors with a thick middle hepatic vein draining the caudal half of the right liver"Trausplautation. 69巻(発表予定). (2000)
[Publications] 李〓、回愛民、他4名: "Altered p_<21>^<WAF1/CIP1 > expression is associated with tumor progression in extrahepatic bile duct carcinomas"Caucer Letters. (発表予定). (2000)
[Publications] 回愛民,他2名: "Cell cycle regulators and human hepatocarcinogenesis"Hepato-Gastroenterology. 45巻. 1635-1642 (1998)
[Publications] 回愛民: "Northern Blotting とRT-PCR"外科. 60巻11号. 1506-1510 (1998)
[Publications] 回愛民.幕内雅俊: "Molecular Genetics of Cancer"BIOS Scientific Publishers (出版予定). (2000)

1999 Fiscal Year Annual Research Report

ヒト肝発癌におけるG1期制御機構異常の役割に関する研究

Principal Investigator

回 愛民 東京大学, 医学部・附属病院, 助手 (70301108)

Research Products

[Publications] 回 愛民,他4名: "Over-expression and lack of retinoblastoma protein are associated with turnor progression and metastasis in hepatocellular carcinoma"International Journal of Cancer. 84巻. 604-608 (1999)

[Publications] 回 愛民,他5名: "Decreased p27^<kip1> expression and cyclin D1 ovexexpression, alone and in combination, influence recurrence and survival of pationts with"Hepatology. 30巻5号. 1167-1173 (1999)

[Publications] 回 愛民,幕内雅敏: "Molecular Basis of Maltistep Hepatocarcinogenesis : Genetic and Epigenetic events"Scandinavian,Journal of Gastroenterology. 8巻. 737-742 (1999)

[Publications] 回 愛民,幕内雅敏: "細胞周期からみた肝癌の悪性度予測"外科. 62巻3号. 293-297 (2000)

[Publications] 回 愛民,他4名: "Loss of p16^<INK4> protein, alone and together with loss of retinoblastoma protein, correlate with hepatocellular carcinoma progression"Cancer Letters. 発表予定. (2000)

[Publications] 史亜州、回愛民、他4名: "Reduced p21^<WAF1/CIP1> protein expression is predominantly related to altered p53 in hepatocellular carcinomas"British Journal of Cancer. 発表予定. (2000)

[Publications] 回 愛民,他5名: "p27^<kip1> expression in normal epithelia, precancerous lesions and carcinomas of the gall- bladder : association with cancer progression"Hepatology. 31巻4号(発表予定). (2000)

[Publications] 回 愛民,他6名: "Left hemihepatectomy in living donors with a thick middle hepatic vein draining the caudal half of the right liver"Trausplautation. 69巻(発表予定). (2000)

[Publications] 李〓、回愛民、他4名: "Altered p_<21>^<WAF1/CIP1 > expression is associated with tumor progression in extrahepatic bile duct carcinomas"Caucer Letters. (発表予定). (2000)

[Publications] 回 愛民,他2名: "Cell cycle regulators and human hepatocarcinogenesis"Hepato-Gastroenterology. 45巻. 1635-1642 (1998)

[Publications] 回 愛民: "Northern Blotting とRT-PCR"外科. 60巻11号. 1506-1510 (1998)

[Publications] 回 愛民.幕内雅俊: "Molecular Genetics of Cancer"BIOS Scientific Publishers (出版予定). (2000)

回愛民東京大学, 医学部・附属病院, 助手 (70301108)

[Publications] 回愛民,他4名: "Over-expression and lack of retinoblastoma protein are associated with turnor progression and metastasis in hepatocellular carcinoma"International Journal of Cancer. 84巻. 604-608 (1999)

[Publications] 回愛民,他5名: "Decreased p27^<kip1> expression and cyclin D1 ovexexpression, alone and in combination, influence recurrence and survival of pationts with"Hepatology. 30巻5号. 1167-1173 (1999)

[Publications] 回愛民,幕内雅敏: "Molecular Basis of Maltistep Hepatocarcinogenesis : Genetic and Epigenetic events"Scandinavian,Journal of Gastroenterology. 8巻. 737-742 (1999)

[Publications] 回愛民,幕内雅敏: "細胞周期からみた肝癌の悪性度予測"外科. 62巻3号. 293-297 (2000)

[Publications] 回愛民,他4名: "Loss of p16^<INK4> protein, alone and together with loss of retinoblastoma protein, correlate with hepatocellular carcinoma progression"Cancer Letters. 発表予定. (2000)

[Publications] 回愛民,他5名: "p27^<kip1> expression in normal epithelia, precancerous lesions and carcinomas of the gall- bladder : association with cancer progression"Hepatology. 31巻4号(発表予定). (2000)

[Publications] 回愛民,他6名: "Left hemihepatectomy in living donors with a thick middle hepatic vein draining the caudal half of the right liver"Trausplautation. 69巻(発表予定). (2000)

[Publications] 回愛民,他2名: "Cell cycle regulators and human hepatocarcinogenesis"Hepato-Gastroenterology. 45巻. 1635-1642 (1998)

[Publications] 回愛民: "Northern Blotting とRT-PCR"外科. 60巻11号. 1506-1510 (1998)

[Publications] 回愛民.幕内雅俊: "Molecular Genetics of Cancer"BIOS Scientific Publishers (出版予定). (2000)