Li Yinghui, Li Fucai, Li-Ling Jesse, Wang Xi, Xu Zhenming, Sun Kailai
Department of Medical Genetics, China Medical University, Shenyang, China.
Cancer Invest. 2005;23(8):660-4. doi: 10.1080/07357900500359836.
Centrosomes regulate cell division by forming bipolar mitotic spindles and, thus, play an essential role in the maintenance of chromosomal stability. Centrosomal amplification has been found commonly among tumor cells. Previous studies have suggested that a STK15 (serine/threonine kinase 15) gene can induce centrosomal amplification, chromosomal instability, and cell transformation. To investigate the role of STK15 gene abnormalities in the occurrence of centrosomal amplification and chromosomal instability, a combinatory approach has been taken to investigate the expression level and point mutations of the STK15 and centrosomal/chromosomal aberrations among 72 cases of laryngeal squamous cell carcinoma and a representative Hep-2 cell line. Although no mutation was detected within its exons 6 or 7, overexpression of STK15 has been found in 47 cases (65 percent) as well as in the Hep-2 cell line; for the latter apparent centrosomal amplification also has been noted, with the number of centrosomes within a single cell varying between 1 and 7 and the proportion of cells with amplified centrosomes reaching 11 approximately 23 percent. Karyotype analysis of Hep-2 cell line has suggested common occurrence of chromosomal aberrations, with the number of chromosomes ranging between 43 and 84, modal number between 69 and 74, and structural aberrations, represented by 13 marker chromosomes, including translocations, deletions, and isochromosomes found in various subclones. Our results suggest that in Hep-2 cell line overexpression of STK15 gene may cause centrosomal amplification thereby result in chromosomal instability through abnormal mitosis. Detection of STK15 overexpression in laryngeal carcinoma has led us to propose that the above may be one of the mechanisms underlying laryngeal carcinogenesis.
中心体通过形成双极有丝分裂纺锤体来调节细胞分裂，因此在维持染色体稳定性方面起着至关重要的作用。中心体扩增在肿瘤细胞中普遍存在。先前的研究表明，STK15（丝氨酸/苏氨酸激酶15）基因可诱导中心体扩增、染色体不稳定和细胞转化。为了研究STK15基因异常在中心体扩增和染色体不稳定发生中的作用，采用了一种联合方法来研究72例喉鳞状细胞癌和一个具有代表性的Hep-2细胞系中STK15的表达水平、点突变以及中心体/染色体畸变情况。虽然在其外显子6或7内未检测到突变，但在47例（65%）病例以及Hep-2细胞系中发现了STK15的过表达；对于后者，也观察到明显的中心体扩增，单个细胞内中心体的数量在1至7个之间变化，中心体扩增的细胞比例约为11%至23%。对Hep-2细胞系的核型分析表明染色体畸变普遍存在，染色体数量在43至84条之间，众数在69至74条之间，并且存在结构畸变，以13条标记染色体为代表，包括在各种亚克隆中发现的易位、缺失和等臂染色体。我们的结果表明，在Hep-2细胞系中，STK15基因的过表达可能导致中心体扩增，从而通过异常有丝分裂导致染色体不稳定。在喉癌中检测到STK15过表达，这使我们提出上述情况可能是喉癌发生的潜在机制之一。
