Expression of platelet-derived growth factor (PDGF)-related transcripts and synthesis of biologically active PDGF-like proteins by human malignant epithelial cell lines.

Expression of platelet-derived growth factor (PDGF)-related transcripts and synthesis of biologically active PDGF-like proteins by human malignant epithelial cell lines.
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人恶性上皮细胞系血小板源性生长因子 (PDGF) 相关转录物的表达和生物活性 PDGF 样蛋白的合成。

DOI:
10.1172/jci113712
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发表时间:
1988
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Pantazis,P
Pantazis,P
中科院分区:
--
文献类型:
--
作者:
Sariban,E;Sitaras,NM;Antoniades,HN;Kufe,DW;Pantazis,P

文献摘要

被引文献

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分析了人恶性上皮细胞系血小板衍生生长因子(PDGF)基因的表达。在测试的12个细胞系中,来自乳腺癌、肺癌、胃癌和卵巢癌的9个细胞系被发现同时表达PDGF-1和PDGF-2基因。当这些细胞被环己亚胺(一种蛋白质合成抑制剂)处理时,PDGF-1和PDGF-2转录本的水平都被超诱导。这些细胞还释放出一种活性,在BALB-c/3T3细胞的研究中,这种活性抑制了125i标记的PDGF的结合,并刺激了[3H]胸苷的结合。用巯基乙醇或PDGF抗体预孵育条件培养基后,这种刺激活性被抑制。此外,这种活性不受热处理的影响。免疫沉淀研究显示,乳腺癌、肺癌和胃癌细胞产生pdgf样蛋白,在非还原条件下迁移为30-和32-kD种,在还原条件下迁移为15-和16-kD种。相比之下,卵巢来源的恶性细胞产生14-16-kD pdgf样蛋白,减少后其流动性不变。由于在这些恶性上皮细胞上未检测到PDGF受体,PDGF样蛋白的产生可能通过旁分泌机制影响微环境中的其他细胞,并可能导致某些癌中出现的过度细胞增殖、炎症反应和结缔组织重塑。图片
Human malignant epithelial cell lines were analyzed for expression of platelet-derived growth factor (PDGF) genes. Of the 12 cell lines tested, 9, derived from breast, lung, gastric, and ovarian carcinomas, were found to express both PDGF-1 and PDGF-2 genes. The levels of both PDGF-1 and PDGF-2 transcripts were superinduced when these cells were treated with cycloheximide, an inhibitor of protein synthesis. These cells also released an activity that in studies with BALB-c/3T3 cells, inhibited binding of 125I-labeled PDGF and stimulated incorporation of [3H]thymidine. This stimulating activity was inhibited after reduction of the conditioned media by mercaptoethanol or after preincubation with antibodies to PDGF. Moreover, this activity was not affected by heat treatment. Immunoprecipitation studies revealed that breast, lung, and gastric carcinoma cells produced PDGF-like proteins that migrated as 30- and 32-kD species under nonreducing conditions and as 15- and 16-kD species under reducing conditions. In contrast, malignant cells of ovarian origin produced 14-16-kD PDGF-like proteins that were unchanged in mobility after reduction. As PDGF receptors were not detected on these malignant epithelial cells, the production of PDGF-like proteins may affect other cells in the microenvironment by paracrine mechanisms and may contribute to excessive cell proliferation, inflammatory reactions, and connective tissue remodeling seen in certain carcinomas.Images