Luteinizing hormone receptor deficiency increases the susceptibility to alkylating agent-induced lymphomagenesis in mice.
Luteinizing hormone receptor deficiency increases the susceptibility to alkylating agent-induced lymphomagenesis in mice.
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黄体生成激素受体缺乏增加了小鼠烷基化剂诱导的淋巴作用的敏感性。
DOI：
10.1007/s12672-010-0045-3
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发表时间：
2010-10
影响因子：
3
通讯作者：
Lei Z
中科院分区：
文献类型：
--
作者：
Yu Y;Yuan F;Li X;Lin D;Lan Z;Rao CV;Lei Z
先前的研究揭示了黄体生成素（LH）/人绒毛膜促性腺激素（hCG）信号传导与性腺和非性腺组织的肿瘤发生之间的密切联系。为了研究 LH 受体 (Lhr) 的基因消除是否影响动物的致癌易感性，对成年雌性野生型 (wt)、杂合子和纯合子 Lhr 敲除 (LhrKO) 小鼠腹腔注射烷化剂 N-甲基-N-亚硝基脲 (MNU，50 毫克/千克体重)。当小鼠呼吸困难时或注射后10个月处死小鼠。结果表明，MNU 分别在杂合子和纯合子动物中诱导 70.6% 和 100% 的非霍奇金胸腺淋巴瘤和淋巴组织淋巴瘤，而在 wt 同胞中，这一比例为 35.7%。肿瘤发展迅速；与 wt 兄弟姐妹相比，Lhr 缺陷小鼠中的它们更具攻击性并转移至脾脏、肝脏和肾脏。所有肿瘤的 T 细胞特异性标记物 CD3 免疫染色呈阳性，但 B 细胞标记物 CD22 免疫染色呈阳性，这表明所有淋巴瘤均源自 T 细胞，而 T 细胞已知为 LH/hCG 受体阳性。 Lhr 基因位点没有重排，各基因型之间的胸腺细胞增殖也没有差异。然而，缺乏 Lhr 的胸腺细胞凋亡较低。 Lhr 杂合子和纯合子动物的胸腺 Bcl-2 水平升高，caspase-3 激活减少。总之，MNU 导致 LhrKO 动物侵袭性淋巴瘤的发病率更高且发病更早，这可能与胸腺细胞凋亡减少有关。
Previous studies have revealed a close link between luteinizing hormone (LH)/human chorionic gonadotropin (hCG) signaling and oncogenesis in gonadal and nongonadal tissues. To investigate whether genetic ablation of LH receptor (Lhr) affects the animal’s oncogenic susceptibility, adult female wild-type (wt), heterozygous, and homozygous Lhr knockout (LhrKO) mice were intraperitoneally injected with an alkylating agent, N-methyl-N-nitrosourea (MNU, 50 mg/kg of body weight). The mice were sacrificed when they were short of breath or 10 months after the injection. The results showed that MNU induced non-Hodgkin’s thymic and lymphonodus lymphomas in 70.6% and 100% of heterozygous and homozygous animals, respectively, compared with 35.7% in wt siblings. The tumor development was rapid; they were more aggressive and metastasized to the spleen, liver, and kidney in Lhr-deficient mice compared to wt siblings. All tumors were immunostained-positive for a T-cell specific marker, CD3, but not for a B-cell marker, CD22, suggesting that all the lymphomas arose from T-cells, which are known to be LH/hCG receptor-positive. There was no rearrangement of the Lhr gene locus or differences in thymic cell proliferation among the genotypes. However, apoptosis was lower in the Lhr-deficient thymuses. The thymic Bcl-2 levels were elevated and caspase-3 activation was reduced in Lhr heterozygous and homozygous animals. In conclusion, MNU induced a higher incidence and an earlier onset of aggressive lymphomas in LhrKO animals, which may be associated with a reduction in apoptosis of thymocytes.