Cytoplasmic transfer of heritable elements other than mtDNA from SAMP1 mice into mouse tumor cells suppresses their ability to form tumors in C57BL6 mice
Cytoplasmic transfer of heritable elements other than mtDNA from SAMP1 mice into mouse tumor cells suppresses their ability to form tumors in C57BL6 mice
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将除 mtDNA 之外的可遗传元件从 SAMP1 小鼠细胞质转移到小鼠肿瘤细胞中，抑制它们在 C57BL6 小鼠中形成肿瘤的能力
DOI：
10.1016/j.bbrc.2017.09.035
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发表时间：
2017
影响因子：
3.1
通讯作者：
Hayashi Jun-Ichi
中科院分区：
文献类型：
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作者：
Shimizu Akinori;Tani Haruna;Takibuchi Gaku;Ishikawa Kaori;Sakurazawa Ryota;Inoue Takafumi;Hashimoto Tetsuo;Nakada Kazuto;Takenaga Keizo;Hayashi Jun-Ichi
在先前的研究中，我们产生了跨线粒体P29mtSAMP1胞质杂交体，其具有来自C57BL6（称为B6）小鼠品系衍生的P29肿瘤细胞的核DNA和从同种异体品系SAMP1外源转移的线粒体DNA（mtDNA）。由于P29mtSAMP1胞质杂交体在同基因B6小鼠中不形成肿瘤，我们提出同种异体SAMP1 mtDNA抑制P29mtSAMP1胞质杂交体的肿瘤形成。为了验证这一假设，本研究通过从P29mtSAMP1胞质杂交体中去除SAMP1 mtDNA并重新引入B6 mtDNA，产生了携带来自同基因B6小鼠的所有基因组（核DNA和mtDNA）的P29mt（sp）B6胞质杂交体。然而，P29mt（sp）B6细胞杂交体在B6小鼠中没有形成肿瘤，即使它们没有SAMP1 mtDNA，这表明SAMP1 mtDNA不参与肿瘤抑制。然后，我们研究了另一种可能性，即SAMP1 mtDNA片段是否潜在地整合到P29mtSAMP1胞质杂交体的核DNA中，从而导致肿瘤抑制。我们通过从P29mt（sp）B6胞质杂交体中去除核DNA并在含有潮霉素的选择培养基中重新引入来自对潮霉素具有抗性的无mtDNA的P29细胞的无整合的SAMP1 mtDNA片段的核DNA来产生P29H（sp）B6胞质杂交体。然而，P29H（sp）B6胞质杂交体在B6小鼠中没有形成肿瘤，即使它们既不携带SAMP1 mtDNA，也不携带整合有SAMP1 mtDNA片段的核DNA。此外，过量产生的活性氧（ROS）和细菌感染不参与肿瘤抑制。这些观察结果表明，肿瘤抑制所造成的mtDNA多态性突变或感染的胞质细菌，但由假设的遗传细胞质元素以外的mtDNA从SAMP 1小鼠。
In a previous study, we generated transmitochondrial P29mtSAMP1 cybrids, which had nuclear DNA from the C57BL6 (referred to as B6) mouse strain-derived P29 tumor cells and mitochondrial DNA (mtDNA) exogenously-transferred from the allogeneic strain SAMP1. Because P29mtSAMP1 cybrids did not form tumors in syngeneic B6 mice, we proposed that allogeneic SAMP1 mtDNA suppressed tumor formation of P29mtSAMP1 cybrids. To test this hypothesis, current study generated P29mt(sp)B6 cybrids carrying all genomes (nuclear DNA and mtDNA) from syngeneic B6 mice by eliminating SAMP1 mtDNA from P29mtSAMP1 cybrids and reintroducing B6 mtDNA. However, the P29mt(sp)B6 cybrids did not form tumors in B6 mice, even though they had no SAMP1 mtDNA, suggesting that SAMP1 mtDNA is not involved in tumor suppression. Then, we examined another possibility of whether SAMP1 mtDNA fragments potentially integrated into the nuclear DNA of P29mtSAMP1 cybrids are responsible for tumor suppression. We generated P29H(sp)B6 cybrids by eliminating nuclear DNA from P29mt(sp)B6 cybrids and reintroducing nuclear DNA with no integrated SAMP1 mtDNA fragment from mtDNA-less P29 cells resistant to hygromycin in selection medium containing hygromycin. However, the P29H(sp)B6 cybrids did not form tumors in B6 mice, even though they carried neither SAMP1 mtDNA nor nuclear DNA with integrated SAMP1 mtDNA fragments. Moreover, overproduction of reactive oxygen species (ROS) and bacterial infection were not involved in tumor suppression. These observations suggest that tumor suppression was caused not by mtDNA with polymorphic mutations or infection of cytozoic bacteria but by hypothetical heritable cytoplasmic elements other than mtDNA from SAMP1 mice.