RECEPTORS FOR HORMONES AND GROWTH-FACTORS AND (ONCO)-GENE AMPLIFICATION IN HUMAN OVARIAN-CANCER
RECEPTORS FOR HORMONES AND GROWTH-FACTORS AND (ONCO)-GENE AMPLIFICATION IN HUMAN OVARIAN-CANCER
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DOI：
10.1002/ijc.2910520211
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发表时间：
1992-09-09
影响因子：
6.4
通讯作者：
FOEKENS, JA
中科院分区：
文献类型：
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作者：
BERNS, EMJJ;KLIJN, JGM;FOEKENS, JA
对卵巢腺癌、交界性肿瘤、良性肿瘤和正常卵巢组织中的受体状态和基因扩增进行了研究。65%（53/82）的卵巢腺癌、57%（8/14）的良性/交界性肿瘤和31%（5/16）的正常卵巢组织显示特异性I-125-EGF（表皮生长因子）结合（中位数：17; 10;和0 fmol EGF-R/mg蛋白），并且在这些组中观察到孕酮受体（PgR）水平显著增加（中位数：分别为5、33和152 fmol/mg蛋白）。EGF-R水平与雌激素受体（ER）或PgR水平之间没有相关性。通过Scatchard分析研究的25例腺癌的所有膜样品均为胰岛素样生长因子- I受体（IGF-I-R）阳性，并且含有比10例正常卵巢组织膜更高的IGF-I-R水平，其中9例为阳性（中位数：分别为64和26 fmol IGF-I-R/mg膜蛋白）。此外，通过放射自显影术测量，37例腺癌组织显示IGF-I-R表达（1.5+至4+）高于10例正常卵巢组织切片（1 +）。I-125-IGF-I结合主要与上皮肿瘤细胞相关，周围结缔组织呈阴性，并且在几个样本中，在肿瘤坏死区域发现IGF-I-R高表达。对25例卵巢腺癌的DNA进行Southern杂交分析，发现IGF-Ⅰ-R和EGF-R基因均未扩增。HER 2/neu基因仅在2/3的组织学证实的类胶质瘤样腺癌中扩增，而在其他22种肿瘤中未扩增。c-myc基因扩增率为28%（7/25）。所有c-myc扩增的肿瘤均为PgR阴性。没有观察到任何研究的基因重排。总之，与良性/交界性卵巢肿瘤和正常卵巢组织相比，在没有基因扩增的情况下，卵巢腺癌组织显示PgR水平降低，IGF-I-R和EGF-R表达增加。此外，c-myc和HER 2/neu基因的扩增，没有这些基因的重排，发生在这些肿瘤的少数。
Receptor status and gene amplification were studied in advanCed human ovarian adenocarcinoma tissues, borderline and benign ovarian tumours and normal ovarian tissues. Sixty-five percent (53/82) of ovarian adenocarcinomas, 57% (8/14) of benign/borderline tumours and only 31% (5/16) of normal ovarian tissues studied showed specific I-125-EGF (epidermal growth factor) binding (median: 17; 10; and 0 fmol EGF-R/mg protein, respectively) and a significant increase in progesterone receptor (PgR) levels was observed in these groups (median: 5; 33; and 152 fmol/mg protein, respectively). No correlations were observed between the levels of EGF-R and the levels of either oestrogen receptors (ER) or PgR. All membrane samples of 25 adenocarcinomas studied by Scatchard analysis were positive for insulin-like growth-factor- I receptors (IGF- I -R) and contained higher IGF-I-R levels than membranes of 10 normal ovarian tissues, of which 9 were positive (median: 64 and 26 fmol IGF-I-R/mg membrane protein, respectively). Also, as measured by autoradiography, 37 adenocarcinoma tissues showed a higher expression of IGF-I-R (1.5+ to 4+) than sections derived from 10 normal ovarian tissues (1 +). I-125-IGF- I binding was predominantly associated with epithelial tumour cells, the surrounding connective tissue was-negative and in several samples high expression of IGF- I -R was found in areas of tumour necrosis. Southern blot analysis of DNAs isolated from 25 ovarian adenocarcinomas revealed no amplification of the IGF- I -R or the EGF-R gene. The HER2/neu gene was amplified only in 2 out of 3 histologically confirmed endometrioid adenocarcinomas studied but not in 22 other tumours. An amplification of the c-myc gene was observed in 28% (7/25) of the tumours. All c-myc-amplified tumours were PgR-negative. No rearrangement was observed for any of the genes studied. In conclusion, ovarian adenocarcinoma tissues show a decrease in PgR levels and an increased expression of IGF- I -R and EGF-R, in the absence of gene amplification, when compared to benign/ borderline ovarian tumours and normal ovarian tissues. In addition, amplification of the c-myc and HER2/neu genes, without rearrangement of these genes, occurs in a minority of these tumours.