IMMORTALIZATION PHENOTYPE DISSOCIATED FROM THE PRENEOPLASTIC PHENOTYPE IN MOUSE MAMMARY EPITHELIAL OUTGROWTHS INVIVO
IMMORTALIZATION PHENOTYPE DISSOCIATED FROM THE PRENEOPLASTIC PHENOTYPE IN MOUSE MAMMARY EPITHELIAL OUTGROWTHS INVIVO
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DOI：
10.1093/carcin/14.1.25
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发表时间：
1993-01-01
期刊：
影响因子：
4.7
通讯作者：
KITTRELL, FS
中科院分区：
文献类型：
--
作者：
MEDINA, D;KITTRELL, FS
从正常处女BALB/c雌性小鼠中分离出小鼠乳腺上皮细胞(MMEC)，在细胞培养中培养不同时间后，将其注射到同系小鼠的乳房脂肪垫中。在注射的MMEC导致的导管突起中，有四个形成了突起，这些突起被连续移植到超过正常导管突起的寿命。正常导管的寿命为五代或六代移植。这四条导管生长系被称为EL，意为延长寿命，已经连续移植了7代、9代、13代和14代。这些突起在形态上以导管为主，不表现导管内上皮增生症的特征，生长依赖于卵巢，对催乳素介导的肺泡分化有反应。其中EL5、EL7、EL11三株未自发成瘤(0/)，二甲基苯并[a]菲(DM[BA])处理后仅1株(1/30)。第四条线EL12与其他三条线不同，存在有限程度的肺泡分化。EL12细胞系未产生任何自发性肿瘤(0/23)，但对DMBA有一定程度的反应(3/10)。我们解释EL系(至少EL11和EL12)代表细胞群体，其中永生化的表型与增殖表型分离，这是小鼠乳腺癌前群体的特征。肿瘤抑制基因P53在EL导管突起中没有过度表达。据我们所知，这是第一个活体内细胞群体永生但其他方面正常的例子。因此，它们可能代表了小鼠乳腺肿瘤发生过程中可观察到的最早阶段，并提供了独特的细胞群体来检查与永生属性相关的分子变化。
Mouse mammary epithelial cells (MMEC) isolated from normal virgin BALB/c female mice and grown in cell culture for various lengths of time were injected into the mammary fat pads of syngenic mice. Of the ductal outgrowths which resulted from the injected MMEC, four gave rise to outgrowths that were serially transplanted beyond the lifetime of normal ductal outgrowths. The lifetime of normal ducts is five or six transplant generations. The four ductal outgrowth lines, termed EL for 'extended life', have been serially transplanted for 7, 9, 13 and 14 transplant generations. The outgrowths are predominately ductal in morphology, do not exhibit intraductal epitheliosis characteristic of ductal hyperplasias, are ovarian dependent for growth and are responsive to prolactin-mediated alveolar differentiation. Three of the EL lines, EL5, 7 and 11 have not produced any tumors spontaneously (0/64) and only one tumor after dimethylbenz[a]anthracene (DM[BA) treatment (1/30). The fourth line, EL12, differs from the other three in the presence of a limited degree of alveolar differentiation. The EL12 line has not produced any spontaneous tumors (0/23) but is somewhat more responsive to DMBA (3/10). We interpret the EL lines (at least EL11 and EL12) to represent cell populations where the immortalized phenotype is dissociated from the hyperplastic phenotype which is characteristic of mouse mammary preneoplastic populations. The tumor suppressor gene, p53, is not overexpressed in the EL ductal outgrowths. To our knowledge, this is the first example of cell populations in vivo that are immortalized but otherwise normal. As such, they may represent the earliest stage observable in the genesis of mouse mammary tumors and provide unique cell populations to examine molecular alterations associated with the property of immortality.