Overexpression of Cancer Stem Cell Markers in Renal Cell Carcinoma
A Matta, S El Jamal, HH Zhang, N Gokden, CY Fan. University of Arkansas for Medical Sciences, Little Rock, AR; John L. McClellan Memorial Veterans Hospital and UAMS, Little Rock, AR
Background: SALL4 and BMI-1 are putative oncogenes that modulate stem cell pluripotency and play a role in oncogenesis of a wide variety of human malignant tumors. Aldehyde dehydrogenase (ALDH) and CD44 have been implicated in multiple biological and biochemical pathways and has been used to identify potential cancer stem cells. In this study, we analyze gene expression levels of these 4 cancer stem cell markers in clear cell renal cell carcinoma (CC-RCC) as compared to matched normal renal parenchyma.
Design: Total RNA was extracted from 14 fresh CC-RCC samples and their matched benign renal parenchyma. Gene expression levels for SALL4, BMI-1, ALDH1A1 and CD44 were analyzed by real-time RT-PCR Quantitation with the ABI Fast 7500 Real-time PCR System using Taqman 18S RNA as an internal control for normalization.
Results: The mRNA expression levels are significantly higher in CC-RCC than those seen in adjacent normal parenchyma in 8 of 14 cases (57%) for the SALL4 gene, 12 of 14 cases (85%) for the BMI-1 gene, 12 of 14 cases (85%) for the ALDH1A1 gene and 11 of 14 cases (78%) for the CD44 gene. Overall, the mRNA expression levels in CC-RCC is about 6 folds for the SALL4 gene, 5 folds for the BMI-1 gene and 3 folds for the ALDH1A1 gene and 4 folds for the CD44 gene, as much as those seen in normal renal tissues. Mean relative mRNA levels for SALL4, BMI-1, ALDH1A1 and CD44 in all 14 tumor cases are 1.2, 4.8, 5.8 and 16.3 respectively as compared to a mean of 0.1, 0.9, 1.7 and 4.8 for normal renal parenchyma.
Conclusions: Significant upregulation of cancer stem cell markers occurs commonly in CC-RCC as compared to matched normal renal parenchyma. These results support a stem cell carcinogenesis theory for clear cell RCC in which the driven force for initiation and progression of a cancer is derived from a small population of cancer stem cells. Therefore, anticancer therapy should aim at eradicating this small population of cancer stem cells.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 108, Wednesday Morning