Matrix metalloproteinase-9 is differentially expressed in nonfunctioning invasive and noninvasive pituitary adenomas and increases invasion in human pituitary adenoma cell line.

摘要: The complete resection of pituitary adenomas (PAs) is unlikely when there an extensive local dural invasion and given that the molecular mechanisms remain primarily unknown. DNA microarray analysis was performed to identify differentially expressed genes between nonfunctioning invasive noninvasive PAs. Gene clustering revealed a robust eightfold increase in matrix metalloproteinase (MMP)-9 expression surgically resected human PAs (nonfunctioning) HP75 tumor-derived cell line treated with phorbol-12-myristate-13-acetate; these results were confirmed by real-time polymerase chain reaction, gelatin zymography, reverse transcriptase-polymerase Western blot, immunohistochemistry, Northern blot analyses. activation protein kinase C (PKC) increased both MMP-9 activity expression, which blocked some PKC inhibitors (Go6976, bisindolylmaleimide, Rottlerin), PKC-α, PKC-δ small interfering (si)RNAs but not hispidin (PKC-β inhibitor). In transmembrane assay, phorbol-12-myristate-13-acetate (100 nmol/L) number invaded cells, process attenuated inhibitors, antibody, PKC-α siRNA, or siRNA. These demonstrate may provide putative therapeutic targets for control PA invasion.