Centrosomes duplicate only once in coordination with the DNA replication cycle and have an important role in segregating genetic material. In contrast, most cancer cells have centrosome aberrations, including supernumerary centrosomes, and this correlates with aneuploidy and genetic instability. The tumor suppressors p16 (CDKN2A) and p15 (CDKN2B) (encoded by the familial melanoma CDKN2 locus) inhibit CDK4/6 activity and have important roles in cellular senescence. p16 is also associated with suppressing centrosomal aberrations in breast cancer; however, the role of p15 in centrosome amplification is unknown. Here, we investigated the relationship between p15 and p16 expression, centrosome number abnormalities, and melanoma progression in cell lines derived from various stages of melanoma progression. We found that normal human melanocyte lines did not exhibit centrosome number abnormalities, whereas those from later stages of melanoma did. Additionally, under conditions of S-phase block, p15 and p16 status determined whether centrosome overduplication would occur. Indeed, removal of p15 from p16-negative cell lines derived from various stages of melanoma progression changed cells that previously would not overduplicate their centrosomes into cells that did. Although this study used cell lines in vitro, it suggests that, during clinical melanoma progression, sequential loss of p15 and p16 provides conditions for centrosome duplication to become deregulated with consequences for genome instability.

中心体在与 DNA 复制周期协调时仅复制一次，并且在分离遗传物质方面具有重要作用。相比之下，大多数癌细胞具有中心体畸变，包括多余的中心体，这与非整倍体和遗传不稳定性有关。肿瘤抑制基因 p16 (CDKN2A) 和 p15 (CDKN2B)（由家族性黑色素瘤CDKN2编码）locus) 抑制 CDK4/6 活性并在细胞衰老中起重要作用。p16 还与抑制乳腺癌的中心体畸变有关；然而，p15 在中心体扩增中的作用尚不清楚。在这里，我们研究了源自黑色素瘤进展不同阶段的细胞系中 p15 和 p16 表达、中心体数量异常和黑色素瘤进展之间的关系。我们发现正常的人类黑色素细胞系没有表现出中心体数量异常，而黑色素瘤晚期的细胞系则表现出中心体数量异常。此外，在 S 期阻滞条件下，p15 和 p16 状态决定了是否会发生中心体过度复制。的确，从黑色素瘤进展的各个阶段衍生的 p16 阴性细胞系中去除 p15 改变了以前不会过度复制其中心体的细胞。尽管这项研究在体外使用了细胞系，但它表明，在临床黑色素瘤进展过程中，p15 和 p16 的连续丢失为中心体复制的失调提供了条件，从而导致基因组不稳定。