Medina Daniel, Kittrell Frances S, Shepard Anne, Stephens L Clifton, Jiang Cheng, Lu Junxuan, Allred D Craig, McCarthy Maureen, Ullrich Robert L
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
FASEB J. 2002 Jun;16(8):881-3. doi: 10.1096/fj.01-0885fje. Epub 2002 Apr 10.
The absence of the tumor suppressor gene p53 confers an increased tumorigenic risk for mammary epithelial cells. In this report, we describe the biological and genetic properties of the p53 null preneoplastic mouse mammary epithelium in a p53 wild-type environment. Mammary epithelium from p53 null mice was transplanted serially into the cleared mammary fat pads of p53 wild-type BALB/c female to develop stable outgrowth lines. The outgrowth lines were transplanted for 10 generations. The outgrowths were ductal in morphology and progressed through ductal hyperplasia and ductal carcinoma in situ before invasive cancer. The preneoplastic outgrowth lines were immortal and exhibited activated telomerase activity. They are estrogen and progesterone receptor-positive, and aneuploid, and had various levels of tumorigenic potential. The biological and genetic properties of these lines are distinct from those found in most hyperplastic alveolar outgrowth lines, the form of mammary preneoplasia occurring in most traditional models of murine mammary tumorigenesis. These results indicate that the preneoplastic cell populations found in this genetically engineered model are similar in biological properties to a subset of precurser lesions found in human breast cancer and provide a unique model to identify secondary events critical for tumorigenicity and invasiveness.
肿瘤抑制基因p53的缺失会增加乳腺上皮细胞的致瘤风险。在本报告中，我们描述了在p53野生型环境中p53缺失的肿瘤前小鼠乳腺上皮的生物学和遗传学特性。将p53缺失小鼠的乳腺上皮连续移植到p53野生型BALB/c雌性小鼠清除后的乳腺脂肪垫中，以建立稳定的生长系。将生长系移植10代。生长物在形态上为导管型，在浸润性癌之前经历导管增生和原位导管癌。肿瘤前生长系是永生的，并表现出端粒酶活性激活。它们雌激素和孕激素受体呈阳性，且为非整倍体，具有不同水平的致瘤潜能。这些系的生物学和遗传学特性与大多数增生性肺泡生长系不同，后者是大多数传统小鼠乳腺肿瘤发生模型中出现的乳腺肿瘤前病变形式。这些结果表明，在这个基因工程模型中发现的肿瘤前细胞群体在生物学特性上与人类乳腺癌中发现的一部分前体病变相似，并提供了一个独特的模型来识别对致瘤性和侵袭性至关重要的二次事件。
