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| Item Type: | Article |
|---|---|
| Title: | Silencing of human ferrochelatase causes abundant protoporphyrin-IX accumulation in colon cancer |
| Creators Name: | Kemmner, W. and Wan, K. and Ruttinger, S. and Ebert, B. and Macdonald, R. and Klamm, U. and Moesta, K.T. |
| Abstract: | Hemes and heme proteins are vital components of essentially every cell of virtually every eukaryote organism. Previously, we demonstrated accumulation of the heme precursor protoporphyrin-IX (PpIX) in gastrointestinal tumor tissues. To elucidate the mechanisms of PpIX accumulation by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we studied expression of the relevant enzymes of the heme synthetic pathway. Here, we describe a significant down-regulation of ferrochelatase (FECH) mRNA expression in gastric, colonic, and rectal carcinomas. Accordingly, in an in vitro model of several carcinoma cell lines, ferrochelatase down-regulation and loss of enzymatic activity corresponded with an enhanced PpIX-dependent fluorescence. Direct detection of PpIX in minute amounts was achieved by a specifically developed pulsed solid-state laser dual delay fluorimetry setup. Silencing of FECH using small interfering RNA (siRNA) technology led to a maximum 50-fold increased PpIX accumulation, imageable by a specifically adapted two-photon microscopy unit. Our results show that in malignant tissue a transcriptional down-regulation of FECH occurs, which causes endogenous PpIX accumulation. Furthermore, accumulation of intracellular PpIX because of FECH siRNA silencing provides a small-molecule-based approach to molecular imaging and molecular therapyKemmner, W., Wan, K., Ruettinger, S., Ebert, B., Macdonald, R., Klamm, U., Moesta, K. T. Silencing of human ferrochelatase causes abundant protoporphyrin-IX accumulation in colon cancer. |
| Keywords: | Heme metabolism, Gastrointestinal carcinomas, siRNA silencing, Cytoplasmatic red fluorescence |
| Source: | FASEB Journal |
| ISSN: | 0892-6638 |
| Publisher: | Federation of American Societies for Experimental Biology |
| Volume: | 22 |
| Number: | 2 |
| Page Range: | 500-509 |
| Date: | February 2008 |
| Official Publication: | https://doi.org/10.1096/fj.07-8888com |
| PubMed: | View item in PubMed |
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