LAT-1 expression in pre- and post-implantation embryos and placenta.
LAT-1 expression in pre- and post-implantation embryos and placenta.
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LAT-1 在植入前和植入后胚胎和胎盘中的表达。
DOI：
10.1016/j.placenta.2008.12.015
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发表时间：
2009-03
期刊：
影响因子：
3.8
通讯作者：
Padbury JF
中科院分区：
文献类型：
--
作者：
Chrostowski MK;McGonnigal BG;Stabila JP;Padbury JF
LAT-1（L 型氨基酸转运蛋白 1）是一种不依赖于 L、Na+ 的氨基酸转运蛋白系统，负责转运大的中性氨基酸。 LAT-1 表达失调是许多原发性人类癌症的特征，并且与肿瘤侵袭有关。培养的原代大鼠肝细胞响应氨基酸消耗而增加 LAT-1 mRNA。转化的肝细胞系表现出 LAT-1 的组成型表达。这些观察结果表明，LAT-1 表达在有限的氨基酸可用性下具有生长和生存优势。 LAT-1 在胎盘中高度表达。先前已经表明，氨基酸是植入前胚胎中细胞功能和能量代谢的基本调节剂。我们的目标是定性和定量分析小鼠胚胎发育植入前阶段的 LAT-1 表达，并鉴定植入后阶段表达 LAT-1 的细胞类型。 LAT-1 通过实时 qPCR 进行定量。通过激光捕获显微切割、原位杂交和免疫组织化学进行表达定位。我们的结果显示，随着胚胎从受精卵发育到囊胚，LAT-1 mRNA 水平不断增加，在孵化囊胚时水平最高。对发育中的小鼠胎盘显微解剖样本进行的 LAT-1 表达研究显示，在植入时 (E7.5)，滋养层巨细胞 (TGC) 中 LAT-1 mRNA 水平最高，其次是母体蜕膜、外胎盘锥和外胚层。在发育后期（E9.5 和 E11.5），未观察到 LAT-1 的差异表达。原位杂交和免疫组织化学也分别显示 LAT-1 mRNA 和蛋白质的差异表达，TGC 的 E7.5 染色最深。到 E9.5 和 E11.5，mRNA 表达不再优先定位于 TGC，不同细胞类型和区域之间的杂交是相等的。然而，LAT-1 蛋白表达在 E9.5 和 E11.5 的 TGC 中仍然显示出最高的染色强度。由于滋养层巨细胞是取代并吞噬子宫上皮细胞的侵袭性细胞，这些数据表明 LAT-1 可能在侵袭性表型中发挥作用。因此，胎盘形成过程中 LAT-1 的调节机制可能为其在肿瘤进展和侵袭中的作用提供有价值的线索。
LAT-1 (L-type amino acid transporter 1) is a system L, Na+-independent amino acid transporter responsible for transport of large neutral amino acids. Dysregulated expression of LAT-1 is characteristic of many primary human cancers and is related to tumor invasion. Primary rat hepatocytes in culture increase LAT-1 mRNA in response to amino acid depletion. Transformed hepatic cell lines demonstrate constitutive expression of LAT-1. These observations suggest that LAT-1 expression confers a growth and survival advantage under limited amino acid availability. LAT-1 is highly expressed in the placenta. It has been shown previously that amino acids are fundamental regulators of cell function and energy metabolism in pre-implantation embryos. Our objectives were to analyze qualitatively and quantitatively LAT-1 expression in pre-implantation stages of mouse embryo development and to identify cell types expressing LAT-1 in post implantation stages. LAT-1 was quantified by real-time qPCR. Localization of expression was by laser capture microdissection, in situ hybridization and immunohistochemistry. Our results show increasing mRNA levels of LAT-1 as the embryo develops from zygote to blastocyst with highest levels at hatching blastocyst. Expression studies of LAT-1 on microdissected samples from developing mouse placenta show highest levels of LAT-1 mRNA in trophoblast giant cells (TGC’s) at the time of implantation (E7.5), followed by maternal decidua, ectoplacental cone and epiblast. At later stages of development (E9.5 and E11.5) no differential expression of LAT-1 was observed. In situ hybridization and immunohistochemistry also showed differential expression of LAT-1 mRNA and protein, respectively, with darkest staining in TGC’s at E7.5. By E9.5 and E11.5 mRNA expression was no longer preferentially localized to TGC’s, hybridization was equal across the different cell types and regions. LAT-1 protein expression, however, still showed highest intensity of staining in TGC’s at E9.5 and E11.5. Since trophoblast giant cells are invasive cells that displace and phagocytose the uterine epithelial cells, these data suggest that LAT-1 may play a role in the invasive phenotype. The mechanism of LAT-1 regulation during placentation, therefore, might provide valuable clues to its role in tumor progression and invasion.
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影响因子：
6.1
作者：
Jones, GM;Trounson, AO;Wood, C
通讯作者：
Wood, C
影响因子：
4.8
作者：
Campbell, WA;Sah, DE;Thompson, NL
通讯作者：
Thompson, NL
影响因子：
6.7
作者：
Gardner, DK;Vella, P;Schoolcraft, WB
通讯作者：
Schoolcraft, WB
DOI：
10.1097/00075197-200101000-00008
发表时间：
2001-01-01
影响因子：
3.1
作者：
Kimball, SR;Jefferson, LS
通讯作者：
Jefferson, LS
影响因子：
4.8
作者：
Mannion, BA;Kolesnikova, TV;Hemler, ME
通讯作者：
Hemler, ME