Enomoto A, Sandgren E P, Maronpot R R
Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
Vet Pathol. 1998 Jul;35(4):283-91. doi: 10.1177/030098589803500407.
To analyze the effects of c-myc and transforming growth factor alpha (TGFalpha) on hepatocarcinogenesis induced by simian virus 40 T antigen (TAg), livers from single and bitransgenic mice, 3 to 11 mice per line, were examined morphologically 1 to 8 weeks after birth. Mice carrying c-myc or TGFalpha alone exhibited centrilobular hypertrophy and increased apoptosis (c-myc mice only) of hepatocytes after 3 or 4 weeks of age, but no detectable changes in cell proliferation or proliferative lesions were observed in either line during the 8 weeks. Mice carrying TAg alone exhibited increased cell proliferation, apoptosis, and dysplasia of hepatocytes with notably high mitotic and apoptotic indices as major changes before development of putative preneoplastic lesions after 4 weeks of age and neoplastic lesions after 6 weeks. In bitransgenic mice coexpressing c-myc or TGFalpha with TAg, nonproliferative lesions and mitotic and apoptotic indices were similar to those in mice carrying TAg alone. In TAg x c-myc bitransgenic mice, however, both preneoplastic and neoplastic lesions developed sooner and grew more rapidly than those in TAg mice, whereas in TAg x TGFalpha bitransgenic mice, rapid tumor growth was the principle observation. Because of the effects of transgene coexpression, livers from TAg x c-myc and TAg x TGFalpha mice had multiple tumors as early as 3 and 6 weeks of age, respectively. The results indicate cooperative functions of c-myc and TGFalpha with TAg during development and/or growth of liver tumors in vivo.
为分析c-myc和转化生长因子α（TGFα）对猿猴病毒40 T抗原（TAg）诱导的肝癌发生的影响，对单转基因和双转基因小鼠（每个品系3至11只小鼠）出生后1至8周的肝脏进行了形态学检查。单独携带c-myc或TGFα的小鼠在3或4周龄后出现中央小叶肥大和肝细胞凋亡增加（仅c-myc小鼠），但在8周内两个品系均未观察到细胞增殖或增殖性病变的可检测变化。单独携带TAg的小鼠在4周龄后出现推定的癌前病变，6周后出现肿瘤性病变，主要变化为细胞增殖增加、凋亡增加以及肝细胞发育异常，有明显高的有丝分裂和凋亡指数。在同时表达c-myc或TGFα与TAg的双转基因小鼠中，非增殖性病变以及有丝分裂和凋亡指数与单独携带TAg的小鼠相似。然而，在TAg x c-myc双转基因小鼠中，癌前病变和肿瘤性病变比TAg小鼠出现得更早且生长更快，而在TAg x TGFα双转基因小鼠中，主要观察到的是肿瘤快速生长。由于转基因共表达的影响，TAg x c-myc和TAg x TGFα小鼠的肝脏分别早在3周龄和6周龄时就有多个肿瘤。结果表明c-myc和TGFα在体内肝脏肿瘤发生和/或生长过程中与TAg具有协同作用。
