Altered growth of a human neuroendocrine carcinoma line after transfection of a major histocompatibility complex class I gene.
Altered growth of a human neuroendocrine carcinoma line after transfection of a major histocompatibility complex class I gene.
复制标题
转染主要组织相容性复合体 I 类基因后，人类神经内分泌癌细胞系的生长发生改变。
DOI：
10.1073/pnas.86.12.4700
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发表时间：
1989
影响因子：
11.1
通讯作者：
Willett,CG
中科院分区：
文献类型：
--
作者：
Sunday,ME;Isselbacher,KJ;Gattoni-Celli,S;Willett,CG
已知主要组织相容性复合体（MHC） I类分子在介导移植肿瘤的排斥反应中作为细胞毒性T细胞的识别元件。我们证明MHC分子除了在抗肿瘤免疫中的经典作用外，在调节肿瘤细胞生长方面可能具有非免疫功能。用小鼠H-2Ld基因转染低水平内源性I类表达的人神经内分泌癌细胞COLO 320。建立了11个独立的稳定克隆，其中4个只含有prv -neo， 7个也含有不同拷贝数的转染的Ld基因。不同克隆在软琼脂中作为菌落生长的能力与Ld抗原的相对表达量密切相关（r = 0.89; P < 0.001）。克隆生成能力的增强与Ld mRNA水平的升高相关性较弱（r = 0.67, P < 0.05）。克隆能力与扩增的c-myc基因或整合的pRSV-neo的相对表达量没有相关性。此外，在裸鼠中，静脉注射10(5)个细胞6周后，Ld抗原表达与转移性肺菌落形成增加有关。这些观察结果与MHC I类抗原可能在调节某些肿瘤细胞的生长潜力方面具有独立于其参与免疫反应的作用的概念是一致的。
The major histocompatibility complex (MHC) class I molecules are known to serve as recognition elements for cytotoxic T cells in mediating the rejection of transplanted tumors. We demonstrate that MHC molecules may have nonimmune functions in modulating tumor cell growth in addition to their classical role in antitumor immunity. A human neuroendocrine carcinoma cell line, COLO 320, with low levels of endogenous class I expression was transfected with the murine H-2Ld gene. Eleven independent stable clones were established, four containing only pRSV-neo and seven also containing varying copy numbers of the transfected Ld gene. The ability of the different clones to grow as colonies in soft agar correlated strongly with the relative amounts of Ld antigen expression (r = 0.89; P less than 0.001). There was a weaker correlation between increased clonogenic ability and higher levels of Ld mRNA (r = 0.67; P less than 0.05). There was no correlation between clonogenic ability and relative expression of amplified c-myc gene or of integrated pRSV-neo. Furthermore, in nude mice, Ld antigen expression was associated with increased formation of metastatic lung colonies 6 weeks after intravenous injection of 10(5) cells. These observations are consistent with the concept that MHC class I antigens may have a role in modulating the growth potential of certain tumor cells independent of their involvement in immune responses.