Establishment of a mammary carcinoma cell line from Syrian hamsters treated with N-methyl-N-nitrosourea.
Establishment of a mammary carcinoma cell line from Syrian hamsters treated with N-methyl-N-nitrosourea.
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DOI：
10.1016/j.canlet.2011.08.003
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发表时间：
2011-12-15
期刊：
影响因子：
9.7
通讯作者：
Kleiner-Hancock, Heather E.
中科院分区：
文献类型：
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作者：
Coburn, Malari A.;Brueggemann, Sabrina;Bhatia, Shilpa;Cheng, Bing;Li, Benjamin D. L.;Li, Xiao-Lin;Luraguiz, Natalia;Maxuitenko, Yulia Y.;Orchard, Elysse A.;Zhang, Songlin;Stoff-Khalili, Mariam A.;Mathis, J. Michael;Kleiner-Hancock, Heather E.
显然，新的乳腺癌模型在开发新的治疗方法方面是必要的。为了应对这一挑战，我们使用化学致癌物N-甲基-N-亚硝脲(MNU)检查了叙利亚仓鼠的乳腺肿瘤形成。单次注射50 mg/kg的MNU可导致60%的癌前病变发生率和20%的乳腺癌发生率。HMAM4A和HMAM4B细胞系来源于MNU诱发的一例原发乳腺肿瘤。原发肿瘤的形态类似于人类乳腺癌中的高级别低分化腺癌。原发肿瘤HER-2/neu和泛角蛋白阳性，细胞角蛋白5/6和p63阴性。当HMAM4B细胞系植入同基因雌性仓鼠皮下时，肿瘤生长速度为50%。从HMAM4B细胞移植到同基因仓鼠体内的肿瘤被进一步在体外繁殖为稳定的细胞系HMAM5。HMAM5细胞在雌性同基因仓鼠体内生长，成瘤率为70%。这些细胞在体外增殖，在软琼脂中形成集落，是非整倍体，染色体模式数为74(叙利亚仓鼠的正常染色体数为44)。为了确定对雌激素受体(ER)的反应性，用增加他莫昔芬浓度的方法检测了细胞增殖试验。HMAM5和人MCF-7(ER阳性)细胞在24 h时表现出相似的下降，但MDA-MB-231(ER阴性)细胞对他莫昔芬处理后的增殖抑制相对不敏感。这些结果表明，HMAM5细胞系可能来自一种腔B亚型的乳腺肿瘤。这些结果也代表了从叙利亚仓鼠获得的第一个乳腺肿瘤细胞系的特征。HMAM5细胞系很可能在开发新的治疗方法方面作为人类乳腺癌的免疫活性模型有用。
Clearly new breast cancer models are necessary in developing novel therapies. To address this challenge, we examined mammary tumor formation in the Syrian hamster using the chemical carcinogen N-methyl-N-nitrosourea (MNU). A single 50 mg/kg intraperitoneal dose of MNU resulted in a 60% incidence of premalignant mammary lesions, and a 20% incidence of mammary adenocarcinomas. Two cell lines, HMAM4A and HMAM4B, were derived from one of the primary mammary tumors induced by MNU. The morphology of the primary tumor was similar to a high-grade poorly differentiated adenocarcinoma in human breast cancer. The primary tumor stained positively for both HER-2/neu and pancytokeratin, and negatively for both cytokeratin 5/6 and p63. When the HMAM4B cell line was implanted subcutaneously into syngeneic female hamsters, tumors grew at a take rate of 50%. A tumor derived from HMAM4B cells implanted into a syngeneic hamster was further propagated in vitro as a stable cell line HMAM5. The HMAM5 cells grew in female syngeneic hamsters with a 70% take rate of tumor formation. These cells proliferate in vitro, form colonies in soft agar, and are aneuploid with a modal chromosomal number of 74 (the normal chromosome number for Syrian hamster is 44). To determine responsiveness to the estrogen receptor (ER), a cell proliferation assay was examined using increasing concentrations of tamoxifen. Both HMAM5 and human MCF-7 (ER positive) cells showed a similar decrease at 24 h. However, MDA-MB-231 (ER negative) cells were relatively insensitive to any decrease in proliferation from tamoxifen treatment. These results suggest that the HMAM5 cell line was likely derived from a luminal B subtype of mammary tumor. These results also represent characterization of the first mammary tumor cell line available from the Syrian hamster. The HMAM5 cell line is likely to be useful as an immunocompetent model for human breast cancer in developing novel therapies.
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