Hansen, Kerrin and Peters, Kristin and Burkert, Christian K. and Brose, Eric and Calvisi, Diego F. and Ehricke, Katrina and Engeler, Maren and Knuth, Elisa and Kroeger, Nils and Lohr, Andrea and Prey, Jessica and Sonke, Jenny and Vakeel, Padmanabhan and Wladasch, Juliane and Zimmer, Jenny and Dombrowski, Frank and Ribback, Silvia (2024) Knockout of the Carbohydrate Responsive Element Binding Protein Enhances Proliferation and Tumorigenesis in Renal Tubules of Mice. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 25 (21): 11438. ISSN 1661-6596, 1422-0067
Full text not available from this repository. (Request a copy)Abstract
Glycogen-storing so-called clear cell kidney tubules (CCTs), precursor lesions of renal cell carcinoma, have been described in diabetic rats and in humans. The lesions show upregulation of the Akt/mTOR-pathway and the related transcription factor carbohydrate responsive element binding protein (ChREBP), which is supposedly pro-oncogenic. We investigated the effect of ChREBP-knockout on nephrocarcinogenesis in streptozotocin-induced diabetic and normoglycemic mice. Diabetic, but not non-diabetic mice, showed CCTs at 3, 6 and 12 months of age. Glycogenosis was confirmed by periodic acid schiff reaction and transmission electron microscopy. CCTs in ChREBP-knockout mice consisted of larger cells and occurred more frequently compared to wildtype mice. Progression towards kidney tumors was observed in both diabetic groups but occurred earlier in ChREBP-knockout mice. Proliferative activity assessed by BrdU-labeling was lower in 1-week-old but higher in 12-month-old diabetic ChREBP-knockout mice. Surprisingly, renal neoplasms occurred spontaneously in non-diabetic ChREBP-knockout, but not non-diabetic wildtype mice, indicating an unexpected tumor-suppressive function of ChREBP. Immunohistochemistry showed upregulated glycolysis and lipogenesis, along with activated Akt/mTOR-signaling in tumors of ChREBP-knockout groups. Immunohistochemistry of human clear cell renal cell carcinomas revealed reduced ChREBP expression compared to normal kidney tissue. However, the molecular mechanisms by which loss of ChREBP might facilitate tumorigenesis require further investigation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DIABETES-MELLITUS; CHREBP; LIPOGENESIS; METABOLISM; CELLS; RISK; RATS; Akt/mTOR; clear cell tubules; glycogen; MLXIPL; nephrocarcinogenesis; proliferation; renal cell carcinoma; streptozotocin; tumor development |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Jan 2026 14:46 |
| Last Modified: | 26 Jan 2026 14:46 |
| URI: | https://pred.uni-regensburg.de/id/eprint/64577 |
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