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Activator protein-2 (AP-2) is a cell type-specific DNA binding transcription factor family.AP-2α,one of the five different isoforms of AP-2,has received much attention because its absence is associated with poor prognosis. Loss of AP-2αexpression has been correlated with progression of melanoma,prostate cancer and colorectal cancer. Down-regulated cytoplasmic AP-2αexpression was consistently seen in high grade and advanced Duke’s stage colon cancer.Recently,Schwartz et al.reported their study on the mechanism by which loss of AP-2αcontributes to colon cancer progression (Oncogene 2007,26:4049-4058).Several colon cancer cell lines were examined for AP- 2αexpression,among which SW480 did not express AP-2αas revealed by RT-PCR and Western blot analysis. Transfection with AP-2αabolished in vivo growth of SW480 cells orthotopically transplanted into the cecal wall of nude mice.Transfecfion with AP-2αto SW480 cells up-regulated E-cadherin expression by direct binding to its promoter sequence as demonstrated by chromatin immunoprecipitation assay.On the contrary,transfection with AP- 2αresulted in significant down-regulation of matrix-metalloproteinase-9 (MMP-9) by zymography and Western blot analysis.Re-expression of AP-2αin SW480 cells resulted in a 4-fold increase in E-cadherin promoter activity and a 5～14-fold decrease in MMP-9 promoter activity,indicating transcriptional regulation of these genes by AP-2α. Thus,the tumor growth inhibitory effect of AP-2αcould be attributed to increased E-cadherin expression and decreased MMP-9 expression.Moreover,the invasiveness of SW480 cells,as examined by their ability to invade through Matrigel-reconstituted basement membrane,was siguificantly inhibited by AP-2αtransfection.To further confirm the role of AP-2αin colon cancer progression,its expression was silenced by siRNA in an AP-2α-positive KM12C colon cancer cells.It resulted in down-regulation of E-cadherin expression,increased expression of MMP- 9,and an increase in invasive potential of KM12C cells.Taken together,the results provide evidence that AP-2αcan be considered as a tumor suppressor gene,its down-regulation may account for progression of colon cancer.
Activator protein-2 (AP-2) is a cell type-specific DNA binding transcription factor family. AP-2α, one of the five different isoforms of AP-2, has received much attention because its absence is associated with poor prognosis. Loss of AP-2α expression has been correlated with progression of melanoma, prostate cancer and colorectal cancer. Down-regulated cytoplasmic AP-2αexpression was consistently seen in high grade and advanced Duke’s stage colon cancer. Recently, Schwartz et al .reported their study on the mechanism by which loss of AP-2αcontributes to colon cancer progression (Oncogene 2007, 26: 4049-4058). Seral colon cancer cell lines were examined for AP-2αexpression, among which SW480 did not express AP-2αas revealed by RT-PCR and Western blot analysis. Transfection with AP-2α abolished in vivo growth of SW480 cells orthotopically transplanted into the cecal wall of nude mice. Transfecfion with AP-2αto SW480 cells up-regulated E-cadherin expression by direct binding to its promoter Sequence as demonstrated by chromatin immunoprecipitation assay. On the contrary, transfection with AP-2αresulted in significant down-regulation of matrix-metalloproteinase-9 (MMP-9) by zymography and Western blot analysis. in a 4-fold increase in E-cadherin promoter activity and a 5 ~ 14-fold decrease in MMP-9 promoter activity, indicating transcriptional regulation of these genes by AP- 2α. Thus, the tumor growth inhibitory effect of AP-2αcould be attributed to increased E-cadherin expression and decreased MMP-9 expression. More over the invasiveness of SW480 cells, as examined by their ability to invade through Matrigel-reconstituted basement membrane, was siguificantly inhibited by AP-2 [alpha] transfection. To further confirm the role of AP-2αin colon cancer progression, its expression was silenced by siRNA in an AP-2α-positive KM12C colon cancer cells. Due resulted in down-regulation of E-cadherin expression, increased expression of MMP-9, and an in crease in invasive potential of KM12C cells. Taken together, the results provide evidence that AP-2αcan be considered as a tumor suppressor gene, its down-regulation may account for progression of colon cancer.