The free monomeric beta subunit of human chorionic gonadotrophin (hCGβ) and the recently identified homodimeric beta-beta subunit (hCGββ) both have autocrine growth effects
The free monomeric beta subunit of human chorionic gonadotrophin (hCGβ) and the recently identified homodimeric beta-beta subunit (hCGββ) both have autocrine growth effects
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DOI：
10.1159/000077719
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发表时间：
2004-01-01
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影响因子：
--
通讯作者：
Iles, RK
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文献类型：
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作者：
Butler, SA;Iles, RK
游离 hCGbeta 的异位产生是上皮性肿瘤中的常见现象，这种现象最初被认为没有生物学意义。然而，现在很明显，hCGbeta 可能通过抑制细胞凋亡来增加细胞数量，从而显着影响肿瘤的发展。最近发现的 hCGbetabeta 同二聚体与胱氨酸结生长因子具有拓扑相似性，被认为是这些新型致瘤反应的重要介体。在本研究中，我们使用尺寸排阻色谱法从 hCGbeta 同二聚体中分离出 hCGbeta 单体，并通过蛋白质印迹证实了分离。使用四唑溴化物掺入细胞数定量测定 (MTT)，我们测量了对应于单体 (hCGbeta) 和二聚体 (hCGbetabeta) 形式的分离 hCGbeta 级分对 hCGbeta 响应细胞系 T24 的生长效果。细胞数量的最大增加对应于二聚体和单体 hCGbeta 的洗脱峰。总之，最近观察到的 hCGbetabeta 同二聚体在刺激膀胱癌细胞生长方面并不比其单体对应物更具生物活性。这强化了以下观点：hCGbeta 可能通过其他胱氨酸结生长因子受体的拮抗抑制来发挥其抗凋亡作用，而不是通过其拓扑对应物 TGF、PDGF-B 和 NGF 中所见的特定受体介导的同二聚体相互作用来发挥其抗凋亡作用。版权所有 (C) 2004 S. Karger AG，巴塞尔。
The ectopic production of free hCGbeta is a common phenomenon in epithelial tumours, a phenomenon originally believed to have no biological significance. However, it is now apparent that hCGbeta may significantly effect tumour development by increasing cell populations through inhibition of apoptosis. The recently identified hCGbetabeta homodimer, with topological similarities to cystine knot growth factors, has been suggested to be the responsible mediator of these novel tumourigenic responses. In this study we isolated hCGbeta monomer from hCGbeta homodimer using size exclusion chromatography and confirmed the separation by Western blotting. Using a tetrazolium bromide incorporation cell number quantification assay (MTT), we measured the growth effects of separated hCGbeta fractions corresponding to monomeric (hCGbeta) and dimeric (hCGbetabeta) forms on the hCGbeta responding cell line T24. Maximal increases in cell number corresponded to the elution peak of dimeric and monomeric hCGbeta. In conclusion, it would appear that the recently observed hCGbetabeta homodimer is no more bioactive than its monomeric counterpart, in stimulating bladder cancer cell growth. This strengthens the proposition that hCGbeta may exert its antiapoptotic effects by antagonistic inhibition of other cystine knot growth factor receptors and not by a specific receptor-mediated homodimeric interaction as seen for its topological counterparts TGF, PDGF-B and NGF. Copyright (C) 2004 S. Karger AG, Basel.