Ozen M, Multani A, Chang S, Voneschenbach A, Chung L, Pathak S
UNIV TEXAS,MD ANDERSON CANC CTR,DEPT CELL BIOL,HOUSTON,TX 77030. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT UROL,HOUSTON,TX 77030. UNIV TEXAS,GRAD SCH BIOMED SCI,HOUSTON,TX 77030.
Int J Oncol. 1996 May;8(5):883-8. doi: 10.3892/ijo.8.5.883.
A positive family history of prostate cancer is a risk factor for this disease, suggesting that alterations of certain genes may play an important role in the development and progression of prostate cancer. However, genetic alterations responsible for initiation and acquisition of metastatic phenotypes by prostate cancer are not well defined. We have observed a consistent change in chromosome 5 in an in vitro cell model of human prostate carcinogenesis in which the near-diploid cells from the surrounding tissue of an adenocarcinoma of the prostate obtained from a 42-year-old patient were subjected to in vitro cell culture and passages. We have examined three different passages of this cell strain by conventional and molecular cytogenetic methods and have seen an increased number of alterations in chromosome 5 in higher passage cells, with accompanying changes in cell morphology. In late passages of this cell line, no cell showed two normal copies of chromosome 5 as analyzed by G-banding and fluorecent in situ hybridization (FISH). The long arm (q) of chromosome 5 was either missing or involved in structural rearrangements. This observation suggests that the q arm of chromosome 5 may carry a tumor suppressor gene(s) that is well-expressed in normal prostate tissue, but when one of these tumor suppressor gene(s) is mutated or deleted and its encoded mRNA and protein are differentially expressed or not expressed at all in the prostate cells, then it may lead to initiation of tumor growth and development. Cytogenetic analyses of early passage cells in this cell strain revealed that approximately 78.8% of metaphases were normal, with a 46,XY chromosome constitution, and 21.2% of cells had clonal alterations mostly of chromosomes 5, 7, 8, 15, 16 and Y. In the middle passages, abnormal cells increased in number (78.26%) and also showed a large number of chromosomal changes. In the late passages, all cells showed structural and numerical abnormalities of the same chromosomes, in addition to some new markers; no cells were found to have a normal karyotype. These chromosomal aberrations could be considered early markers of prostate carcinogenesis. Some of the markers present in late passage cells were similar to those reported in a well-characterized prostate cancer cell line, LNCaP.
前列腺癌的家族史是该疾病的一个风险因素，这表明某些基因的改变可能在前列腺癌的发生和发展中起重要作用。然而，导致前列腺癌起始和获得转移表型的基因改变尚未明确。我们在人前列腺癌发生的体外细胞模型中观察到5号染色体的一致变化，该模型中，从一名42岁患者的前列腺腺癌周围组织获取的近二倍体细胞进行了体外细胞培养和传代。我们通过传统和分子细胞遗传学方法检查了该细胞系的三个不同传代阶段，发现较高传代细胞中5号染色体的改变数量增加，同时细胞形态也有相应变化。在该细胞系的后期传代中，通过G显带和荧光原位杂交（FISH）分析，没有细胞显示出5号染色体的两个正常拷贝。5号染色体的长臂（q）要么缺失，要么参与了结构重排。这一观察结果表明，5号染色体的q臂可能携带一个在正常前列腺组织中表达良好的肿瘤抑制基因，但当这些肿瘤抑制基因之一发生突变或缺失，其编码的mRNA和蛋白质在前列腺细胞中差异表达或根本不表达时，可能会导致肿瘤生长和发展的起始。对该细胞系早期传代细胞的细胞遗传学分析显示，约78.8%的中期细胞正常，染色体组成为46,XY，21.2%的细胞有克隆性改变，主要涉及5、7、8、15、16和Y染色体。在中期传代中，异常细胞数量增加（78.26%），并且还显示出大量的染色体变化。在后期传代中，所有细胞除了一些新的标记外，都显示出相同染色体的结构和数量异常；没有发现细胞具有正常核型。这些染色体畸变可被视为前列腺癌发生的早期标记。后期传代细胞中出现的一些标记与在特征明确的前列腺癌细胞系LNCaP中报道的标记相似。
