Zogopoulos G, Albrecht S, Pietsch T, Alpert L, von Schweinitz D, Lefèbvre Y, Goodyer C G
Department of Medicine, McGill University, Montreal, Quebec, Canada.
Cancer Res. 1996 Jul 1;56(13):2949-53.
Eight different 5'-untranslated region variants of the human growth hormone receptor (hGHR) mRNA have been identified in adult liver (V1-V8). We have compared the expression of two of these variants (V1 and V3) in several human fetal and postnatal tissues (including liver) as well as in hepatoblastomas (HBs) and hepatocellular carcinomas (HCCs). Using reverse transcription-PCR assays, followed by Southern blotting to confirm the specificity of the amplified fragments, we found that V3 was expressed in all fetal and postnatal liver (n = 13 fetal and 5 postnatal), kidney (n = 4 fetal and 4 postnatal), lung (n = 4 fetal and 2 postnatal), intestine (n = 8 fetal and 4 postnatal), skeletal muscle (n = 1 fetal and 1 postnatal), and adrenal (n = 1 fetal and 1 postnatal) samples. In contrast, V1 was expressed only in postnatal liver. We then screened for V1 and V3 in HBs (n = 17, ages 6-36 months, including 5 with paired normal liver), and HCCs (n = 4, ages 50-75 years, with paired normal liver). V1 was undetectable in 15 of 17 HBs, including all HBs paired with (V1-expressing) normal liver; the absence of V1 did not correlate with patient age, sex, HB subtype, +/- chemotherapy, exon 3-retaining and -deficient hGHR mRNA isoform pattern, or loss of heterozygosity at 11p, 1p, and 1q. The four HCCs showed marked (>20-fold; n = 2) or complete (n = 2) suppression of V1 as compared to paired normal liver. V3 was expressed in all HBs, HCCs, and paired normal livers. Interestingly, V3, but not V1, was detected in two Wilms' tumor and paired normal kidney specimens. Our findings suggest that, in the human, there is tissue-, fetal- and tumor-specific regulation of V1 hGHR mRNA.
在成人肝脏中已鉴定出人类生长激素受体（hGHR）mRNA的8种不同的5'-非翻译区变体（V1-V8）。我们比较了其中两种变体（V1和V3）在几种人类胎儿和出生后组织（包括肝脏）以及肝母细胞瘤（HBs）和肝细胞癌（HCCs）中的表达情况。通过逆转录-聚合酶链反应（RT-PCR）检测，随后进行Southern印迹以确认扩增片段的特异性，我们发现V3在所有胎儿和出生后肝脏（13例胎儿和5例出生后）、肾脏（4例胎儿和4例出生后）、肺（4例胎儿和2例出生后）、肠（8例胎儿和4例出生后）、骨骼肌（1例胎儿和1例出生后）以及肾上腺（1例胎儿和1例出生后）样本中均有表达。相比之下，V1仅在出生后肝脏中表达。然后我们在肝母细胞瘤（n = 17，年龄6-36个月，包括5例配对正常肝脏）和肝细胞癌（n = 4，年龄50-75岁，配对正常肝脏）中筛查V1和V3。在17例肝母细胞瘤中的15例中未检测到V1，包括所有与（表达V1的）正常肝脏配对的肝母细胞瘤；V1的缺失与患者年龄、性别、肝母细胞瘤亚型、是否接受化疗、外显子3保留和缺失的hGHR mRNA异构体模式以及在11p、1p和1q处的杂合性缺失均无关。与配对的正常肝脏相比，4例肝细胞癌中有2例V1显著抑制（>20倍；n = 2），2例完全抑制（n = 2）。V3在所有肝母细胞瘤、肝细胞癌以及配对的正常肝脏中均有表达。有趣的是，在2例Wilms瘤及配对的正常肾脏标本中检测到了V3，但未检测到V1。我们的研究结果表明，在人类中，V1 hGHR mRNA存在组织、胎儿和肿瘤特异性调控。
