BACKGROUND: High mobility group box l (HMGB1), a nuclear and extracellular protein, is implicated in some physiologic and pathologic conditions. In this study, we investigated the expression and function of HMGB1 in ovarian cancer. METHODS: cDNA microarray analysis was performed to compare gene expression profiles of the highly invasive and the low invasive subclones derived from the SKOV3 human ovarian cancer cell line. Immunohistochemistry (IHC) staining was performed to investigate HMGB1 expression in a total of 100 ovarian tissue specimens. In functional assays, effects of HMGB1 knockdown on the biological behavior of ovarian cancer cells were investigated. RESULTS: HMGB1 was overexpressed in the highly invasive subclone compared with the low invasive subclone. High HMGB1 expression was associated with poor clinicopathologic features. Knockdown of HMGB1 expression significantly suppressed ovarian cancer cell proliferation accompanied by decreased cyclin D1 and PCNA expression, and inhibited cell migration and invasion accompanied by decreased MMP2 and MMP9 activities. CONCLUSION: HMGB1 is a newly identified gene overexpressed in ovarian cancer and associated with poor clinicopathologic features. HMGB1 may serve as a new biomarker and a therapeutic target for ovarian cancer in the future.
BACKGROUND:High mobility group box l (HMGB1), a nuclear and extracellular protein, is implicated in some physiologic and pathologic conditions. In this study, we investigated the expression and function of HMGB1 in ovarian cancer. METHODS: cDNA microarray analysis was performed to compare gene expression profiles of the highly invasive and the low invasive subclones derived from the SKOV3 humanovarian cancer cell line. Immunohistochemistry (IHC) staining was performed to investigate HMGB1 expression in a total of 100 ovarian tissue specimens. In functional assays, effects of HMGB1 knockdown on the biological behavior of ovarian cancer cells were investigated. RESULTS:HMGB1 was overexpressed in the highly invasive subclone compared with the low invasive subclone. High HMGB1 expression was associated with poor clinicopathologic features. Knockdown of HMGB1 expression significantly suppressed ovarian cancer cell proliferation accompanied by decreased cyclin D1 and PCNA expression, and inhibited cell migration and invasion accompanied by decreased MMP2 and MMP9 activities. CONCLUSION:HMGB1 is a newly identified gene overexpressed in ovarian cancer and associated with poor clinicopathologic features. HMGB1 may serve as a new biomarker and a therapeutic target for ovarian cancer in the future.
Authors: Dinç Süren; Mustafa Yıldırım; Özlem Demirpençe; Vildan Kaya; Arsenal Sezgin Alikanoğlu; Nurullah Bülbüller; Mustafa Yıldız; Cem Sezer Journal: Med Sci Monit Date: 2014-03-31