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v-Ha-ras癌基因的导入诱导培养的人甲状腺髓样癌细胞分化。

Introduction of v-Ha-ras oncogene induces differentiation of cultured human medullary thyroid carcinoma cells.

作者信息

Nakagawa T, Mabry M, de Bustros A, Ihle J N, Nelkin B D, Baylin S B

出版信息

Proc Natl Acad Sci U S A. 1987 Aug;84(16):5923-7. doi: 10.1073/pnas.84.16.5923.

DOI:10.1073/pnas.84.16.5923
PMID:3112776
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC298975/
Abstract

Medullary thyroid carcinoma (MTC) is an endocrine tumor of the thyroid C cells that expresses high levels of the neuroendocrine peptide hormone calcitonin. During tumor progression in the host, there is an apparent loss of differentiation in MTC cells that involves a consistent decrease in calcitonin content of the tumor cells associated with decreased expression of the calcitonin gene and/or changes in a mRNA alternative-processing pattern away from that characteristic of the parent thyroid C cell. We now report that introduction of the viral Harvey ras (v-Ha-ras) oncogene into cultured human MTC cells can reverse such changes in gene expression and can induce endocrine differentiation of the tumor cells. The expression of v-Ha-ras is associated with decreased cellular proliferation and DNA synthesis. There is a marked increase in the number of cytoplasmic secretory granules that are a classic feature of differentiated thyroid C cells. v-Ha-ras expression induces increased expression of the calcitonin gene and the processing of the primary gene transcript is shifted to favor calcitonin mRNA rather than calcitonin-gene-related peptide (CGRP) mRNA production. These studies with cultured human MTC cells provide a model system to study the role of Ha-ras and related genes in neuroendocrine differentiation. The findings suggest an important approach for identifying genes in solid tumors whose altered expression may play a role in the impaired maturational capacity characteristic of cancer cells during tumor progression.

摘要

甲状腺髓样癌（MTC）是一种甲状腺C细胞的内分泌肿瘤，其表达高水平的神经内分泌肽激素降钙素。在宿主体内肿瘤进展过程中，MTC细胞明显出现分化丧失，这涉及肿瘤细胞中降钙素含量持续下降，与降钙素基因表达降低和/或mRNA可变加工模式的改变有关，这种改变偏离了亲代甲状腺C细胞的特征模式。我们现在报告，将病毒哈维鼠肉瘤病毒癌基因（v-Ha-ras）导入培养的人MTC细胞中，可以逆转这种基因表达变化，并能诱导肿瘤细胞的内分泌分化。v-Ha-ras的表达与细胞增殖和DNA合成减少有关。作为分化型甲状腺C细胞典型特征的细胞质分泌颗粒数量显著增加。v-Ha-ras表达诱导降钙素基因表达增加，并且初级基因转录本的加工偏向于有利于降钙素mRNA而非降钙素基因相关肽（CGRP）mRNA的产生。这些对培养的人MTC细胞的研究提供了一个模型系统，以研究Ha-ras及相关基因在神经内分泌分化中的作用。这些发现提示了一种重要方法，可用于鉴定实体瘤中的基因，其表达改变可能在肿瘤进展过程中癌细胞成熟能力受损方面发挥作用。

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本文引用的文献

1
AN UNIDENTIFIED VIRUS WHICH CAUSES THE RAPID PRODUCTION OF TUMOURS IN MICE.一种能在小鼠体内迅速引发肿瘤的未识别病毒。
Nature. 1964 Dec 12;204:1104-5. doi: 10.1038/2041104b0.
2
The prognostic and biological significance of cellular heterogeneity in medullary thyroid carcinoma: a study of calcitonin, L-dopa decarboxylase, and histaminase.甲状腺髓样癌中细胞异质性的预后及生物学意义：降钙素、L-多巴脱羧酶和组胺酶的研究
J Clin Endocrinol Metab. 1982 Feb;54(2):233-40. doi: 10.1210/jcem-54-2-233.
3
Human medullary thyroid carcinoma in culture provides a model relating growth dynamics, endocrine cell differentiation, and tumor progression.
Mol Endocrinol. 2014 Dec;28(12):1999-2011. doi: 10.1210/me.2014-1168.
4
Growth arrest signaling of the Raf/MEK/ERK pathway in cancer.癌症中Raf/MEK/ERK信号通路的生长阻滞信号
Front Biol (Beijing). 2014 Feb;9(2):95-103. doi: 10.1007/s11515-014-1299-x.
5
The Role of STAT3 in Thyroid Cancer.STAT3 在甲状腺癌中的作用。
Cancers (Basel). 2014 Mar 6;6(1):526-44. doi: 10.3390/cancers6010526.
6
Noncatalytic function of ERK1/2 can promote Raf/MEK/ERK-mediated growth arrest signaling.ERK1/2 的非催化功能可促进 Raf/MEK/ERK 介导的生长抑制信号。
J Biol Chem. 2009 Nov 27;284(48):33006-18. doi: 10.1074/jbc.M109.012591. Epub 2009 Oct 5.
7
Modeling thyroid cancer in the mouse.在小鼠中模拟甲状腺癌。
Horm Metab Res. 2009 Jun;41(6):488-99. doi: 10.1055/s-0029-1215572. Epub 2009 Apr 8.
8
ZM336372, a Raf-1 activator, causes suppression of proliferation in a human hepatocellular carcinoma cell line.ZM336372，一种Raf-1激活剂，可抑制人肝癌细胞系的增殖。
J Gastrointest Surg. 2008 May;12(5):852-7. doi: 10.1007/s11605-008-0495-x.
9
The Ras/Raf/MEK/extracellular signal-regulated kinase pathway induces autocrine-paracrine growth inhibition via the leukemia inhibitory factor/JAK/STAT pathway.Ras/Raf/MEK/细胞外信号调节激酶通路通过白血病抑制因子/JAK/STAT通路诱导自分泌-旁分泌生长抑制。
Mol Cell Biol. 2003 Jan;23(2):543-54. doi: 10.1128/MCB.23.2.543-554.2003.
10
Roles of trk family neurotrophin receptors in medullary thyroid carcinoma development and progression.Trk家族神经营养因子受体在甲状腺髓样癌发生发展中的作用
Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4540-5. doi: 10.1073/pnas.96.8.4540.
培养的人甲状腺髓样癌提供了一个与生长动力学、内分泌细胞分化和肿瘤进展相关的模型。
J Clin Endocrinol Metab. 1984 Aug;59(2):338-43. doi: 10.1210/jcem-59-2-338.
4
BALB and Kirsten murine sarcoma viruses alter growth and differentiation of EGF-dependent balb/c mouse epidermal keratinocyte lines.BALB和 Kirsten鼠肉瘤病毒改变了依赖表皮生长因子的balb/c小鼠表皮角质形成细胞系的生长和分化。
Cell. 1983 Feb;32(2):599-606. doi: 10.1016/0092-8674(83)90479-8.
5
BALB- and Harvey-murine sarcoma virus transformation of a novel lymphoid progenitor cell.新型淋巴祖细胞的BALB和哈维鼠肉瘤病毒转化
J Exp Med. 1982 Sep 1;156(3):873-87. doi: 10.1084/jem.156.3.873.
6
Alternative RNA processing in calcitonin gene expression generates mRNAs encoding different polypeptide products.降钙素基因表达过程中的可变RNA加工产生编码不同多肽产物的mRNA。
Nature. 1982 Jul 15;298(5871):240-4. doi: 10.1038/298240a0.
7
Inhibitors of glycosylation reverse retroviral interference.糖基化抑制剂可逆转逆转录病毒干扰。
Virology. 1982 May;119(1):185-92. doi: 10.1016/0042-6822(82)90075-7.
8
Harvey and Kirsten sarcoma viruses promote the growth and differentiation of erythroid precursor cells in vitro.哈维肉瘤病毒和柯尔斯滕肉瘤病毒在体外可促进红系前体细胞的生长和分化。
Cell. 1981 Oct;26(1 Pt 1):91-7. doi: 10.1016/0092-8674(81)90036-2.
9
Guanine nucleotide-binding and autophosphorylating activities associated with the p21src protein of Harvey murine sarcoma virus.与哈维鼠肉瘤病毒的p21src蛋白相关的鸟嘌呤核苷酸结合和自身磷酸化活性。
Nature. 1980 Oct 23;287(5784):686-91. doi: 10.1038/287686a0.
10
Dual evolutionary origin for the rat genetic sequences of Harvey murine sarcoma virus.哈维鼠肉瘤病毒大鼠基因序列的双重进化起源
J Virol. 1980 Nov;36(2):408-20. doi: 10.1128/JVI.36.2.408-420.1980.