Abstract: TH-PO895
In Vivo Evidence of Role of Diabetes in Accelerating Kidney Tumorigenesis
Session Information
- Diabetic Kidney Disease: Basic - I
October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Author
- Habib, Samy L., UTHSCSA, San Antonio, Texas, United States
Background
Our published clinical data show a strong risk of diabetes in increasing of renal cell carcinoma in a cohort study of kidney cancer patients whereas 25.4 % of kidney cancer patients have history of diabetes and our recent clinical data showed that RCC patients with history of diabetes increased by 33.3%. The increasing incidence of diabetes in our population will increase the risk of solid tumors including renal cell carcinoma (RCC). The mechanism by which diabetes enhances certain pathways to develop kidney tumor is largely unknown.
Methods
The inherited renal tumor was identified in TSC2+/- animal model, which is naturally heterozygous for mutation in tumor suppressor genes, Tuberous Sclerosis Complex (TSC). The majority of tumors observed in the kidney of TSC2+/- mice originate from renal proximal tubules develop around age of 12 months. We have generated a new mouse model of TSC2+/-/dbdb-/- by cross breed TSC2+/- and dbdb mice to investigate whether diabetes accelerates tumors in new mouse model at early ages.
Results
At the day of sacrificing, WT and TSC2+/- mice showed normal blood glucose levels (80-109 mg/dL), while db/db and TSC2+/-/dbdb mice showed ranges of hyperglycemia between 405-510mg/dL measured by Glucometer in overnight fasting animals. Our novel in vivo data showed for the first time that diabetes accelerates kidney tumor size to 4-fold and number to 2-fold in TSC2+/-/dbdb new mouse model compared to TSC2+/- mice at 10 months old. Data show that no significant difference in tumor size and number between TSC2+/-/dbdb and TSC2+/- mice at age of 8 months. We didn’t recognize any tumor in WT and db/db mice at this age. Next, we performed RNA sequencing in RNA isolated from kidney cortex of WT, db/db, TSC2+/- and TSC2+/-/dbdb mice at age of 10 months. The sequencing data show different patterns of downregulation and upregulation of several genes between TSC2+/-/dbdb, TSC2+/- and dbdb compared to WT mice that have significant interest in regulation of tumorigenesis.
Conclusion
Our data provided in vivo evidence of role of diabetes in accelarting kidney tumorigeneis. These data suggest that short term of diabetes is not effective to enhance tumorigenesis in TSC2+/-/dbdb mice and longer exposure to hyperglycemia is required to initiate tumorigenesis. These data confirmed for the first time that diabetes is a major risk factor for increasing kidney cancer.
Funding
- Veterans Affairs Support