title: STK15 gene overexpression, centrosomal amplification, and chromosomal instability in the absence of STK15 mutations in laryngeal carcinoma.
abstract: 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.
authors.affiliation: Department of Medical Genetics, China Medical University, Shenyang, China.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Li
authors.forename: Fucai
authors.initials: F
authors.lastname: Li
authors.forename: Jesse
authors.initials: J
authors.lastname: Li-Ling
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.forename: Zhenming
authors.initials: Z
authors.lastname: Xu
authors.forename: Kailai
authors.initials: K
authors.lastname: Sun
mesh_terms: D064096:Aurora Kinase A; D064127:Aurora Kinases; D018385:Centrosome / Q000473:pathology*; D043171:Chromosomal Instability; D005091:Exons / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology*; D009154:Mutation / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases