Mincione G, Cirafici A M, Lazzareschi D, Pepe S, Ciardiello F, Colletta G
Istituto di Patologia Umana e Medicina Sociale, Facoltà di Medicina e Chirurgia, Chieti, Italy.
Cancer Res. 1993 Nov 15;53(22):5548-53.
Amplification of erbB-2 gene and overexpression of gp185erbB-2 gene product is found in approximately one-third of primary human breast and ovarian cancer. Overexpression of gp185erbB-2 was recently found in human papillary thyroid carcinomas, but not in thyroid follicular carcinomas or adenomas. The erbB-2 gene encodes a cell surface growth factor receptor with intrinsic tyrosine kinase activity. Wild type human erbB-2 has been shown to act as a potent oncogene when overexpressed in mouse fibroblasts. To test whether overexpression of normal human erbB-2 gene can transform epithelial differentiated rat thyroid cells, these cells were infected with a recombinant retroviral expression vector containing the erbB-2 protooncogene. Rat thyroid cells expressing high levels of gp185erbB-2 do not display a fully transformed and tumorigenic phenotype. However, the isolated cell clones that overexpress gp185erbB-2, show changes in their growth properties if compared to normal thyroid cells, since they can grow in absence of thyrotropin, the main growth factor controlling thyroid cell proliferation in vitro, and do not respond to the growth inhibitory effect of transforming growth factor beta.
在大约三分之一的原发性人类乳腺癌和卵巢癌中发现了erbB - 2基因扩增和gp185erbB - 2基因产物的过表达。最近在人类乳头状甲状腺癌中发现了gp185erbB - 2的过表达，但在甲状腺滤泡癌或腺瘤中未发现。erbB - 2基因编码一种具有内在酪氨酸激酶活性的细胞表面生长因子受体。野生型人类erbB - 2在小鼠成纤维细胞中过表达时已被证明可作为一种有效的癌基因。为了测试正常人erbB - 2基因的过表达是否能转化上皮分化的大鼠甲状腺细胞，这些细胞被含有erbB - 2原癌基因的重组逆转录病毒表达载体感染。表达高水平gp185erbB - 2的大鼠甲状腺细胞未表现出完全转化和致瘤表型。然而，与正常甲状腺细胞相比，过表达gp185erbB - 2的分离细胞克隆显示出其生长特性的变化，因为它们可以在缺乏促甲状腺激素（体外控制甲状腺细胞增殖的主要生长因子）的情况下生长，并且对转化生长因子β的生长抑制作用无反应。
