Use of glycolytic pathways for inhibiting or measuring oncogenic signaling
View Patent ↗Disclosed are methods in which glucose metabolism is correlated to oncogenesis through certain specific pathways; inhibition of certain enzymes is shown to interfere with oncogenic signaling, and measurement of certain enzyme levels is correlated with patient survival. The present methods comprise measuring level of expression of at least one of the enzymes involved in glucose uptake or metabolism, wherein increased expression of the at least one of the enzymes relative to expression in a normal cell correlates with poor prognosis of disease in a patient. Preferably the genes whose expression level is measured include GLUT3, PFKP, GAPDH, ALDOC, LDHA and GFPT2. Also disclosed are embodiments directed towards downregulating the expression of some genes in glucose uptake and metabolism.
1. A method, comprising:
measuring an expression level of at least one cellular marker selected from the group consisting of: platelet-type phosphofructokinase (PFKP); glyceraldehyde-3-phosphate dehydrogenase (GAPDH); aldolase (ALDO); lactate dehydrogenase A (LDHA); glucose transporter 3 (GLUT3); and glutamine-fructose-6-phosphate transaminase (GFPT), in a cell suspected of having increased oncogenic signaling; and
determining whether the measured expression level of said at least one cellular marker in said cell suspected of having increased oncogenic signaling is increased relative to the expression level of said at least one cellular marker in a reference cell.
2. The method of claim 1 further comprising measuring the expression level of at least one of epidermal growth factor receptor (EGFR) and integrin beta 1 (ITGB1).
3. The method of claim 1 wherein said measuring an expression level consists of measuring the expression level of PFKP, GAPDH, ALDO and LDHA.
4. The method of claim 1 wherein said measuring consists of measuring a level of GLUT3.
5. The method of claim 1 wherein said measuring an expression level comprises the step of measuring the expression of mRNA encoding protein corresponding to a marker.
6. The method of claim 1 wherein said expression level is determined by use of a microarray containing nucleic acids hybridizing to a cellular marker being measured.
7. The method of claim 1 wherein said expression level is measured by a method selected from the group consisting of Northern blotting, serial analysis of gene expression (SAGE), and reverse transcription polymerase chain reaction (rt-PCR).
8. The method of claim 1 wherein said measuring an expression level comprises measuring a protein level.
9. The method of claim 8 wherein said measuring a protein level comprises contacting a cellular marker with an antibody specific for said cellular marker.
10. The method of claim 8 wherein said measuring is done by a method selected from the group consisting of ELISA and Western blot.
11. The method of claim 8 wherein said protein level is determined by isotope-coded affinity tags (ICAT).
12. The method of claim 1 wherein expression level of at least three markers is measured.
13. The method of claim 1 wherein said cell suspected of having increased oncogenic signaling is a human cell.
14. The method of claim 13 wherein said cell suspected of having increased oncogenic signaling is a breast epithelial cell.
15. The method of claim 14 wherein said cell suspected of having increased oncogenic signaling is a tumor cell.