Molinolo A, Simian M, Vanzulli S, Pazos P, Lamb C, Montecchia F, Lanari C
Instituto de Biología y Medicina Experimental, Academia Nacional de Medicina, Buenos Aires, Argentina.
Cancer Lett. 1998 Apr 10;126(1):49-57. doi: 10.1016/s0304-3835(97)00527-2.
In previous papers we have demonstrated that sialoadenectomy inhibited MPA-induced mammary tumorigenesis in BALB/c mice. To further explore the role of EGF in this experimental model, we evaluated its effects on mammary glands of sialoadenectomized (sialox) MPA-treated female mice and on tumor growth. MPA-treated sialox mice were injected s.c. (n = 3) or not (n = 6) with 5 microg EGF every 36 h for 45 days; MPA-treated sham-operated mice were used as controls (n = 6). Mammary glands from sialox MPA-treated mice are considerably less developed as compared with sham-operated animals. The exogenous administration of EGF restores the usual MPA-induced growth pattern of the glands, thus confirming a role for EGF either in mediating or cooperating with MPA in inducing the mammary architectural changes observed in MPA-treated mice. On the other hand, primary cultures of progestin-dependent (PD) ductal mammary adenocarcinoma in vivo tumor lines and of lobular progestin-independent (PI) tumor lines were used to evaluate the effect of EGF on tumor growth. In vitro EGF was found to stimulate cell proliferation of lobular PI tumor cells and of fibroblastic cells from both types of tumors at concentrations higher than 0.1-0.5 ng/ml and in the presence of 1-5% of charcoal-stripped fetal calf serum. Conversely, no proliferative effects were observed in ductal PD cells under the same experimental conditions, regardless of the presence of 10 nM MPA. It can be concluded that although EGF plays an important role in MPA-induced mammary carcinogenesis, it is not necessary in PD tumor growth.
在之前的论文中，我们已经证明，唾液腺切除术可抑制BALB/c小鼠中MPA诱导的乳腺肿瘤发生。为了进一步探究EGF在该实验模型中的作用，我们评估了其对唾液腺切除（sialox）且经MPA处理的雌性小鼠乳腺以及肿瘤生长的影响。对经MPA处理的sialox小鼠，每36小时皮下注射（n = 3）或不注射（n = 6）5微克EGF，持续45天；将经MPA处理的假手术小鼠用作对照（n = 6）。与假手术动物相比，经MPA处理的sialox小鼠的乳腺发育明显较差。外源性给予EGF可恢复腺体通常由MPA诱导的生长模式，从而证实EGF在介导MPA或与MPA协同作用以诱导在经MPA处理的小鼠中观察到的乳腺结构变化方面发挥作用。另一方面，使用孕激素依赖性（PD）导管乳腺腺癌体内肿瘤系和小叶孕激素非依赖性（PI）肿瘤系的原代培养物来评估EGF对肿瘤生长的影响。在体外，发现EGF在浓度高于0.1 - 0.5纳克/毫升且存在1 - 5%活性炭处理胎牛血清的情况下，可刺激小叶PI肿瘤细胞以及两种肿瘤的成纤维细胞的细胞增殖。相反，在相同实验条件下，无论是否存在10纳摩尔MPA，导管PD细胞均未观察到增殖效应。可以得出结论，尽管EGF在MPA诱导的乳腺癌发生中起重要作用，但在PD肿瘤生长中并非必需。
