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首页> 美国卫生研究院文献>British Journal of Cancer >A prolactin-dependent metastasising rat mammary carcinoma as a model for endocrine-related tumour dormancy.
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A prolactin-dependent metastasising rat mammary carcinoma as a model for endocrine-related tumour dormancy.

机译：催乳素依赖性转移性大鼠乳腺癌作为内分泌相关肿瘤休眠的模型。

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In order to study the growth kinetics of breast tumours during long-term hormonal withdrawal, we developed a transplantable, invasive mammary carcinoma EMR-86 that originated in a female WAG/Olac rat bearing a subcutaneously implanted oestrogen pellet (EP). Outgrowth of transplanted tumours occurs only in the presence of an EP, and metastases are formed in lungs and regional lymph nodes. Subsequent EP removal induces rapid regression. However, tumours do not disappear completely, as small nodules persist. These dormant tumour remnants can be restimulated even after long periods. Because EP-stimulated tumours regressed after treatment with bromocriptine and dormant tumours in non-oestrogenized rats grew out after treatment with perphenazine, prolactin is the major growth-stimulating hormone in this model. Cell kinetics in the growing, regressing and dormant phase were studied by immunocytochemical detection of DNA-incorporated bromodeoxyuridine (BrdUrd) in tissue sections. BrdUrd labelling indices decreased from 21.6 +/- 3.0% to less than 1% within 7 days after EP removal. After prolonged hormonal withdrawal (up to 90 days) BrdUrd-labelled tumour cells could always be demonstrated (range 0.4-0.8%), without a concomitant increase in tumour volume. Additional treatment either with bromocriptine or with ovariectomy could not significantly reduce this residual proliferative activity, as demonstrated by continuous BrdUrd labelling experiments. The results indicate that in vivo dormancy may represent a steady state of cell division and cell loss, rather than an accumulation of cells in a non-cycling G0 state.
机译：为了研究长期激素戒断期间乳腺肿瘤的生长动力学，我们开发了一种可移植的浸润性乳腺癌EMR-86，其起源于雌性WAG / Olac大鼠，其皮下植入了雌激素颗粒（EP）。仅在存在EP的情况下才会发生移植肿瘤的生长，并且在肺和区域淋巴结中形成转移灶。随后的EP移除会导致快速消退。然而，由于小结节持续存在，肿瘤并未完全消失。这些休眠的肿瘤残留物即使经过很长时间也可以重新刺激。因为在用溴隐亭治疗后，EP刺激的肿瘤消退了，在未雌激素的大鼠中，用奋乃静治疗后，休眠的肿瘤长大了，催乳素是该模型中主要的促生长激素。通过组织切片中掺入DNA的溴脱氧尿苷（BrdUrd）的免疫细胞化学检测，研究了生长期，退化期和休眠期的细胞动力学。去除EP后7天内，BrdUrd标记指数从21.6 +/- 3.0％下降至不足1％。长时间撤激素（长达90天）后，始终可以显示BrdUrd标记的肿瘤细胞（范围为0.4-0.8％），而不会伴随肿瘤体积的增加。连续的BrdUrd标记实验表明，溴隐亭或卵巢切除术的其他治疗均不能显着降低这种残留的增殖活性。结果表明体内休眠可能代表细胞分裂和细胞丢失的稳定状态，而不是处于非循环G0状态的细胞积累。

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