TITLE
Generation of Human Cell Lines with Inactivated GLUT1 Genes
CASE NUMBER
C11819
INVENTION NOVELTY
Tangible material involving generation of mutant isogenic, cancerous cell lines RKO and DLD1 disrupted alleles for GLUT1 protein by homologous recombination.
VALUE PROPOSITION
This tangible material can serve as an important research tool for studying the fundamental attributes of the micro-environments surrounding cancerous cells. The modified cell lines can be used for the following applications:
• Studying the physiological micro-environmental conditions that provide selective advantage for cells carrying either BRAF or KRAS mutations to clonally expand.
• Studying the relationship between hypoxia and hypoglycemia in cancerous micro-environments.
TECHNICAL DETAILS
Johns Hopkins researchers have developed a modified form of the adenocarcinoma cell lines RKO and DLD1 in which both the alleles encoding for the glucose transporter protein GLUT-1 were disrupted by homologous recombination. These cells were used as a negative control in studying the mutually exclusive effects of BRAF and KRAS mutations on the up-regulation of GLUT-1 transporter and subsequently the rate of glucose uptake by cancerous cells. Using this tangible material, it was found that the increase in GLUT1 transcription was unrelated to the transcription factor Hypoxia Inducible Factor 1 alpha (HIF 1 alpha). The relationship between hypoxia and hypoglycemia in cancerous micro-environments was also studied, with the former condition favoring the selection of cells with KRAS or BRAF mutations, whereas the latter favors the selection of cells with PIK3CA, CMYC, or TP53 mutations.
STAGE OF DEVELOPMENT
Tangible material, Human GLUT1 (-/-) DLD-1 Cell Line
ASSOCIATED PUBLICATION
Science. 2009 Sep 18; 325(5947): 1555.
