Checkpoint Kinase 1 Is Overexpressed during HPV16-Induced Cervical Carcinogenesis

Abstract

Purpose: Cervical cancer is one of the leading causes of cancer death among women worldwide. Checkpoint kinase 1 (Chk1) has a critical role in DNA damage response and cell cycle checkpoint control. Emerging evidence suggests that Chk1 promotes tumor growth. However, whether Chk1 is important for development of cervical cancer is largely unknown. Methods: The levels of Chk1 mRNA expression were determined using quantitative real-time polymerase chain reaction in a panel of 90 cervical specimens, including 30 cervical cancer tissues, 30 CIN II–III, and 30 normal cervical tissues. We investigated the correlation between Chk1 and HPV16 E6/E7 at the mRNA level using another 30 CIN II–III and 32 cervical cancer tissues with HPV16 infection. MTT and cell cycle assays were conducted to show the function role of Chk1 in cervical cancer SiHa cells. Results: Chk1 was gradually increased during cervical lesion progression and positively correlated with HPV16 E6/E7 expression. Inhibition of Chk1 resulted in suppressed cell proliferation concomitant with the blocking of cell cycle at S-phase in cervical cancer SiHa cells. Conclusions: These results indicate that maintained Chk1 expression by HPV16 E6/E7 in cervical cancer cells promotes cell growth by blocking the cell cycle progression, and may point to novel strategies for targeting Chk1 in cancer therapy.