Oakley C S, Welsch M A, Zhai Y F, Chang C C, Gould M N, Welsch C W
Department of Pharmacology/Toxicology, Michigan State University, East Lansing 48824.
Int J Cancer. 1993 Apr 1;53(6):1002-7. doi: 10.1002/ijc.2910530624.
Grafts of primary carcinogen (DMBA)-induced mammary carcinomas from Sprague-Dawley rats have a poor transplantation efficiency in athymic nude mice. Further compromising these mice immunologically via whole-body irradiation and/or splenectomy, or the administration of hormonal growth factors (estrogen and progesterone) to these mice, did not significantly alter transplantation efficiency. Use of strains of mice that are more immune-impaired than the athymic nude mouse, i.e., the athymic nude-beige-XID mouse (T-cell and LAK-cell deficient) or mice with severe combined immune deficiency (SCID) (which lack functional T cells and B cells) also failed to improve transplantation efficiency. In contrast, transplantation efficiency was sharply increased when primary neu-induced rat mammary carcinomas from female Sprague-Dawley rats were used. These mammary carcinomas, unlike the DMBA-induced rat mammary carcinomas, have a very high level of expression of neu; transplantation of these tumors to either athymic nude mice or SCID mice was considerably more efficient. Thus, these data provide evidence that enhanced expression of neu confers heightened efficiency in the transplantation of primary rat mammary carcinomas to immune-deficient mice (athymic-nude or SCID). Increased neu expression was a greater determinant than more compromised immune states in the transplantation of these rat mammary carcinomas. This biological characteristic of neu expression in mammary carcinomas provides new, additional insight into the importance of this oncogene in mammary tumorigenic processes and may explain, at least in part, the reported inverse relationship between human breast carcinoma neu expression and patient prognosis.
将源自斯普拉格 - 道利大鼠的原发性致癌物（二甲基苯并蒽，DMBA）诱导的乳腺癌移植到无胸腺裸鼠中时，移植效率较低。通过全身照射和/或脾切除术对这些小鼠进行进一步的免疫抑制，或者给这些小鼠施用激素生长因子（雌激素和孕酮），均未显著改变移植效率。使用比无胸腺裸鼠免疫功能更受损的小鼠品系，即无胸腺裸 - 米色 - XID小鼠（T细胞和淋巴因子激活的杀伤细胞缺陷）或严重联合免疫缺陷（SCID）小鼠（缺乏功能性T细胞和B细胞），也未能提高移植效率。相比之下，当使用源自雌性斯普拉格 - 道利大鼠的原发性neu诱导的大鼠乳腺癌时，移植效率急剧提高。与DMBA诱导的大鼠乳腺癌不同，这些乳腺癌中neu的表达水平非常高；将这些肿瘤移植到无胸腺裸鼠或SCID小鼠中效率要高得多。因此，这些数据表明，neu表达的增强赋予了原发性大鼠乳腺癌移植到免疫缺陷小鼠（无胸腺裸鼠或SCID）中的效率提高。在这些大鼠乳腺癌的移植中，neu表达增加比免疫状态更受损是一个更大的决定因素。乳腺癌中neu表达的这一生物学特性为该癌基因在乳腺肿瘤发生过程中的重要性提供了新的额外见解，并且至少可以部分解释报道的人类乳腺癌neu表达与患者预后之间的负相关关系。
