Augmented release of matrix metalloproteinase-9 by PKC activation in organotypic cultures of human breast cancer and adjacent normal breast tissue and fibroadenoma.
The organotypic culture technique and quantitative gelatin zymography were used to determine the expression of matrix metalloproteinase (MMP)-9 and MMP-2 in human breast cancer and adjacent normal breast tissue and fibroadenoma. MMP-9 and MMP2 were constitutively expressed in all cultures. The release of these two enzymes in breast cancer was higher than that in adjacent normal breast tissue and fibroadenoma. Administration of 12-o-tetradecanoyl- phorbol-13-acetate (TPA) increased the release of MMP-9 but not of MMP-2. This response was inhibited by protein kinase C (PKC) inhibitor (H7), transcription inhibitor (actinomycin D) and translation inhibitor (cycloheximide). Moreover, the increased level of MMP-9 by TPA in breast cancer was also higher than that in adjacent normal breast tissue and fibroadenoma. These phenomena were also observed in the DAG-treated culture. These findings suggested that the MMP-9 expression in the breast cancer tissue may be more sensitive for the PKC activation.
Wu
Trang-Tiau
TT
Department of Surgery, School of Medicine, Medical College, Chung Shan Medical University, Taichung 402, Taiwan.
Tsai
Jen-Hsiang
JH
Tsai
Ju-Hsin
JH
Kuo
Shou-Jen
SJ
Yu
Shi-Yau
SY
Huang
Chih-Yang
CY
Hsieh
Hai-Yung
HY
Hsieh
Yih-Shou
YS
Liu
Jer-Yuh
JY
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D001940:Breast / Q000201:enzymology*; D001943:Breast Neoplasms / Q000201:enzymology*; D003208:Concanavalin A / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D020536:Enzyme Activators / Q000494:pharmacology; D005260:Female; D018226:Fibroadenoma / Q000201:enzymology*; D005780:Gelatin / Q000378:metabolism; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D009924:Organ Culture Techniques; D011480:Protease Inhibitors / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D020536:Enzyme Activators; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D011500:Protein Synthesis Inhibitors; D003208:Concanavalin A; D003609:Dactinomycin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D005780:Gelatin; D003513:Cycloheximide; D011493:Protein Kinase C; D020780:Matrix Metalloproteinase 9