Siegrist S, Féral C, Chami M, Solhonne B, Mattéi M G, Rajpert-De Meyts E, Guellaën G, Bulle F
INSERM U99, Hôpital H. Mondor, 94010 Créteil, France.
Oncogene. 2001 Aug 23;20(37):5155-63. doi: 10.1038/sj.onc.1204658.
By systematic analysis of a human testis library, we have isolated the hH-Rev107-3 cDNA, identical to hH-Rev107-1 cDNA, which was previously described as a class II tumor suppressor gene. In this study, two transcripts (1 and 0.8 kb) were detected by Northern blot in all human tissues, excepted in thymus. The strongest expression was found in testis, skeletal muscle and heart. These two mRNA are probably transcribed from only one gene that we mapped to the q12-q13 region of the chromosome 11. In human testis, hH-Rev107 gene expression was localized, by in situ hybridization, within the round spermatids. To investigate a possible role for hH-Rev107 protein in testicular malignant growth, we examined the expression of this gene in germ cell tumors. A strong hH-Rev107 gene expression was observed in normal testis as well as in samples with preinvasive carcinoma in situ but was completely absent in overt tumors, both seminomas and non-seminomas. By in situ hybridization, CIS was found hH-Rev107 positive and tumor negative. A semi-quantitative assessment of hH-Rev107 mRNA level in testicular germ cell tumors, by RT-PCR, exhibited a ninefold decrease in the gene expression. No gross structural aberrations of hH-Rev107 gene were detected in these human primary tumors. The results suggest that down-regulation of hH-Rev107 may be associated with invasive progression of testicular germ cell tumors.
通过对人类睾丸文库进行系统分析，我们分离出了hH-Rev107-3 cDNA，它与hH-Rev107-1 cDNA相同，hH-Rev107-1 cDNA先前被描述为II类肿瘤抑制基因。在本研究中，通过Northern印迹法在除胸腺外的所有人类组织中检测到两种转录本（1和0.8 kb）。在睾丸、骨骼肌和心脏中发现最强的表达。这两种mRNA可能仅从一个基因转录而来，我们将该基因定位于11号染色体的q12-q13区域。在人类睾丸中，通过原位杂交，hH-Rev107基因表达定位于圆形精子细胞内。为了研究hH-Rev107蛋白在睾丸恶性生长中的可能作用，我们检测了该基因在生殖细胞肿瘤中的表达。在正常睾丸以及原位癌前病变样本中观察到强烈的hH-Rev107基因表达，但在明显的肿瘤（精原细胞瘤和非精原细胞瘤）中完全不存在。通过原位杂交，原位癌（CIS）呈hH-Rev107阳性而肿瘤呈阴性。通过RT-PCR对睾丸生殖细胞肿瘤中hH-Rev107 mRNA水平进行半定量评估，结果显示基因表达下降了9倍。在这些人类原发性肿瘤中未检测到hH-Rev107基因的明显结构异常。结果表明，hH-Rev107的下调可能与睾丸生殖细胞肿瘤的侵袭性进展有关。
