Natali P G, Nicotra M R, Digiesi G, Cavaliere R, Bigotti A, Trizio D, Segatto O
Regina Elena Cancer Institute, Rome, Italy.
Int J Cancer. 1994 Feb 1;56(3):341-6. doi: 10.1002/ijc.2910560308.
Over-expression of the HER-2 oncogene correlates with poor prognosis in breast and ovarian carcinomas. Using a sensitive immunohistochemical assay, we have detected low levels of gp185HER-2 in intradermal nevi (78%) and in primary (75%) and metastatic melanomas (58%). The HER-2 gene product expressed by cultured melanoma cells had the expected molecular weight, but no levels of tyrosine phosphorylation could be detected. Consistently, we were unable to inhibit in vitro growth of melanoma cells with an anti-gp 185HER-2 MAb, in conditions in which the growth of SKBr-3 breast-carcinoma cells was severely impaired. However, immunotoxins to gp 185HER-2 were able to kill gp185HER-2-positive melanoma cells. These data indicate that low levels of gp185HER-2 are expressed by the melanocyte lineage, with no correlation with transformation or tumor progression. Nevertheless, gp185HER-2 appears a suitable target for immunotherapy of cutaneous melanoma.
HER-2癌基因的过度表达与乳腺癌和卵巢癌的不良预后相关。通过一种敏感的免疫组织化学检测方法,我们在皮内痣(78%)、原发性黑色素瘤(75%)和转移性黑色素瘤(58%)中检测到低水平的gp185HER-2。培养的黑色素瘤细胞表达的HER-2基因产物具有预期的分子量,但未检测到酪氨酸磷酸化水平。同样,在SKBr-3乳腺癌细胞生长受到严重抑制的条件下,我们无法用抗gp 185HER-2单克隆抗体抑制黑色素瘤细胞的体外生长。然而,针对gp 185HER-2的免疫毒素能够杀死gp185HER-2阳性的黑色素瘤细胞。这些数据表明,黑色素细胞系表达低水平的gp185HER-2,与细胞转化或肿瘤进展无关。尽管如此,gp185HER-2似乎是皮肤黑色素瘤免疫治疗的合适靶点。