Bussemakers M J, van de Ven W J, Debruyne F M, Schalken J A
Department of Urology, Radboud University Hospital, Nijmegen, The Netherlands.
Cancer Res. 1991 Jan 15;51(2):606-11.
One of the major problems in the diagnosis of localized prostatic tumors is to predict the aggressiveness of an individual tumor, which is presumably associated with chance to progression. In an attempt to find molecular markers that are specific for aggressive prostatic cancer cells, we compared steady-state mRNA levels of progressionally related prostatic tumors. The Dunning R-3327-H subline, a relatively benign rat prostatic tumor, was compared to the therefrom derived highly aggressive MatLyLu tumor by differential hybridization analysis. The differential screening revealed 26 complementary DNA clones that detected transcripts overexpressed in MatLyLu. Upon further screening on the entire panel of Dunning R-3327 sublines, it appeared that three clones (pBUS1, pBUS19, and pBUS30), detected transcripts specifically expressed in metastatic rat prostatic tumors. The expression pattern of pBUS19 and pBUS30 suggested a relation between these complementary DNAs. Nucleotide sequence analysis, however, could not yet substantiate this. Computer-assisted comparison of the DNA sequences revealed the presence of rat long terminal repeat-like repetitive elements in pBUS19. The differential expression of repetitive elements in progressionally related tumors is interesting, yet similar findings have not been reported in human malignancies. Nucleotide sequence analysis of pBUS1 indicated that this clone is identical or related to high mobility group protein I(Y), a non-histone nuclear protein. From recent studies it appeared that this protein might be implicated in replication and/or transcription processes and is induced in fast proliferating/undifferentiated cells. The overexpression of high mobility group protein I(Y) correlates rather with metastatic ability than with growth rate; hence it may serve as a valuable marker to identify progressionally advanced prostate cancer cells.
局限性前列腺肿瘤诊断中的一个主要问题是预测单个肿瘤的侵袭性，这可能与肿瘤进展的几率相关。为了寻找侵袭性前列腺癌细胞特有的分子标志物，我们比较了进展相关前列腺肿瘤的稳态mRNA水平。通过差异杂交分析，将相对良性的大鼠前列腺肿瘤邓宁R-3327-H亚系与由此衍生的高侵袭性MatLyLu肿瘤进行了比较。差异筛选揭示了26个互补DNA克隆，这些克隆检测到在MatLyLu中过度表达的转录本。在对整个邓宁R-3327亚系进行进一步筛选时，发现三个克隆（pBUS1、pBUS19和pBUS30）检测到在转移性大鼠前列腺肿瘤中特异性表达的转录本。pBUS19和pBUS30的表达模式表明这些互补DNA之间存在关联。然而，核苷酸序列分析尚未证实这一点。对DNA序列进行计算机辅助比较发现，pBUS19中存在大鼠长末端重复样重复元件。进展相关肿瘤中重复元件的差异表达很有趣，但在人类恶性肿瘤中尚未有类似报道。pBUS1的核苷酸序列分析表明，该克隆与高迁移率族蛋白I(Y)相同或相关，高迁移率族蛋白I(Y)是一种非组蛋白核蛋白。从最近的研究来看，这种蛋白可能与复制和/或转录过程有关，并且在快速增殖/未分化细胞中被诱导。高迁移率族蛋白I(Y)的过度表达与转移能力的相关性大于与生长速率的相关性；因此，它可能是识别进展性晚期前列腺癌细胞的一个有价值的标志物。
