Weber K L, Bolander M E, Rock M G, Pritchard D, Sarkar G
Mayo Clinic, Department of Orthopaedic Surgery, Rochester, Minnesota 55905, USA.
J Orthop Res. 1998 Jan;16(1):8-14. doi: 10.1002/jor.1100160103.
Little is known about bone and cartilage tumors at the molecular level; thus, the identification of genes associated with these tumors may be useful as markers and therapeutic targets. To address this issue and to test the hypothesis that abnormal expression of one or more growth factors in the transforming growth factor-beta superfamily is associated with musculoskeletal neoplasia, degenerate primers based on the conserved sequences in these genes were made for screening tumor samples by reverse transcription-polymerase chain reaction. First, these primers were used to obtain a comparative profile between a low-grade chondrosarcoma and its dedifferentiated high-grade counterpart in the same patient. This experiment identified an amplified DNA product in the high-grade sample that was identical to osteogenic protein-1/bone morphogenetic protein-7. Osteogenic protein-1 mRNA expression was 17-fold greater in this high-grade sample than in the low-grade one. Osteogenic protein-1 was highly expressed (three of three) in human osteosarcoma cell lines but was not expressed (zero of four) in normal osteoblast samples. Screening for gene expression of osteogenic protein-1 in 57 osteosarcomas and chondrosarcomas indicated that 44% (range: 38-52%) of them were positive for osteogenic protein-1 mRNA. Screening of breast and prostate tumors revealed a similar association with osteogenic protein-1 mRNA expression.
在分子水平上，人们对骨和软骨肿瘤了解甚少；因此，鉴定与这些肿瘤相关的基因可能作为标志物和治疗靶点。为了解决这个问题并检验转化生长因子-β超家族中一种或多种生长因子的异常表达与肌肉骨骼肿瘤形成相关的假设，基于这些基因的保守序列制备了简并引物，用于通过逆转录-聚合酶链反应筛选肿瘤样本。首先，这些引物被用于获取同一患者低级别软骨肉瘤与其去分化高级别对应物之间的比较图谱。该实验在高级别样本中鉴定出一种扩增的DNA产物，其与成骨蛋白-1/骨形态发生蛋白-7相同。该高级别样本中成骨蛋白-1 mRNA表达比低级别样本高17倍。成骨蛋白-1在人骨肉瘤细胞系中高表达（3/3），但在正常成骨细胞样本中不表达（0/4）。对57例骨肉瘤和软骨肉瘤进行成骨蛋白-1基因表达筛查表明，其中44%（范围：38-52%）的样本成骨蛋白-1 mRNA呈阳性。对乳腺和前列腺肿瘤的筛查显示，其与成骨蛋白-1 mRNA表达也有类似关联。
