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РЖ ВИНИТИ 76 (BI29) 96.11-04Н1.126

Laird, A. Douglas
Inhibition of tumor growth in liver epithelial cells transfected with a transforming growth factor 'альфа' antisense gene [Text] / A.Douglas Laird, Pamela I. Brown, Nelson Fausto // Cancer Res. - 1994. - Vol. 54, N 15. - P4224-4232 . - ISSN 0008-5472
Перевод заглавия: Подавление роста опухолевых эпителиальных клеток печени при трансфекции геном трансформирующего фактора роста 'альфа' в антисмысловой ориентации
Аннотация: Transforming growth factor 'альфа' (TGF'альфа') overexpression is associated with human hepatocellular carcinoma and with transformation of rat liver epithelial cell lines. In transgenic mice TGF'альфа' overexpression in the liver induces hepatocyte proliferation and leads to the development of tumors. Using a transformed rat liver epithelial cell line which can give rise to hepatocellular carcinomas, we used antisense genes to examine the importance of TGF'альфа' in tumor growth. Two different rat TGF'альфа' complementary DNA fragments were cloned in the antisense orientation into a thymidine kinase minigene downstream of a retroviral long terminal repeat. Cell lines that stably expressed the more effective construct, which contained a fragment that spanned the TGF'альфа' start codon, exhibited a 4-fold reduction in TGF'альфа' secretion relative to cell lines that expressed the thymidine kinase minigene alone. Following introduction into nude mice of 2*10{5} cells the control cell lines grew rapidly to produce large, highly cellular tumors by 5-6 weeks following injection, whereas with the antisense cell lines tumor growth was delayed so that tumors needed an additional 5 weeks to reach the same size. A high level of growth inhibition was also evident following injection of 2*10{6} cells, although the delay in tumor growth from antisense lines was shortened to about 3 weeks. Furthermore, tumors produced by 3 of the 4 antisense cell lines tested were fibrotic and hypocellular relative to those produced by the control cell lines. Growth of tumors from the antisense cell lines was associated with a decline in antisense RNA expression. In contrast, tumors generated from the control cell lines maintained high levels of expression of the control thymidine kinase minigene. These data demonstrate that tumor growth from highly tumorigenic liver cells can be inhibited by disrupting their ability to produce TGF'альфа'. [F. N.], Brown Univ., Dep. of Pathology, Lab. Medicine, Providence, RI 02912. Библ. 61

ГРНТИ	76.29.49

ВИНИТИ 761.29.49.03.25.25
Рубрики: ТРАНСФОРМИРОВАННЫЕ КЛЕТКИ
ЭПИТЕЛИЙ
ПЕЧЕНЬ
РОСТ НА ГОЛЫХ МЫШАХ
ФАКТОРЫ РОСТА
ФАКТОР ТРАНСФОРМИРУЮЩИЙ АЛЬФА
ГЕН В АНТИСМЫСЛОВОЙ ОРИЕНТАЦИИ

Доп.точки доступа:
Brown, Pamela I.; Fausto, Nelson

РЖ ВИНИТИ 76 (BI28) 96.12-04Н3.260

Laird, A. Douglas
Inhibition of tumor growth in liver epithelial cells transfected with a transforming growth factor 'альфа' antisense gene [Text] / A.Douglas Laird, Pamela I. Brown, Nelson Fausto // Cancer Res. - 1994. - Vol. 54, N 15. - P4224-4232 . - ISSN 0008-5472
Перевод заглавия: Подавление роста опухолевых эпителиальных клеток печени при трансфекции геном трансформирующего фактора роста 'альфа' в антисмысловой ориентации
Аннотация: Transforming growth factor 'альфа' (TGF'альфа') overexpression is associated with human hepatocellular carcinoma and with transformation of rat liver epithelial cell lines. In transgenic mice TGF'альфа' overexpression in the liver induces hepatocyte proliferation and leads to the development of tumors. Using a transformed rat liver epithelial cell line which can give rise to hepatocellular carcinomas, we used antisense genes to examine the importance of TGF'альфа' in tumor growth. Two different rat TGF'альфа' complementary DNA fragments were cloned in the antisense orientation into a thymidine kinase minigene downstream of a retroviral long terminal repeat. Cell lines that stably expressed the more effective construct, which contained a fragment that spanned the TGF'альфа' start codon, exhibited a 4-fold reduction in TGF'альфа' secretion relative to cell lines that expressed the thymidine kinase minigene alone. Following introduction into nude mice of 2*10{5} cells the control cell lines grew rapidly to produce large, highly cellular tumors by 5-6 weeks following injection, whereas with the antisense cell lines tumor growth was delayed so that tumors needed an additional 5 weeks to reach the same size. A high level of growth inhibition was also evident following injection of 2*10{6} cells, although the delay in tumor growth from antisense lines was shortened to about 3 weeks. Furthermore, tumors produced by 3 of the 4 antisense cell lines tested were fibrotic and hypocellular relative to those produced by the control cell lines. Growth of tumors from the antisense cell lines was associated with a decline in antisense RNA expression. In contrast, tumors generated from the control cell lines maintained high levels of expression of the control thymidine kinase minigene. These data demonstrate that tumor growth from highly tumorigenic liver cells can be inhibited by disrupting their ability to produce TGF'альфа'. [F. N.], Brown Univ., Dep. of Pathology, Lab. Medicine, Providence, RI 02912. Библ. 61

ГРНТИ	76.29.49

ВИНИТИ 761.29.49.55.15
Рубрики: ТРАНСФОРМИРОВАННЫЕ КЛЕТКИ
ЭПИТЕЛИЙ
ПЕЧЕНЬ
РОСТ НА ГОЛЫХ МЫШАХ
ФАКТОРЫ РОСТА
ФАКТОР ТРАНСФОРМИРУЮЩИЙ АЛЬФА
ГЕН В АНТИСМЫСЛОВОЙ ОРИЕНТАЦИИ

Доп.точки доступа:
Brown, Pamela I.; Fausto, Nelson

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