Cancer type-specific tNOX isoforms: A putative family of redox protein splice variants with cancer diagnostic and prognostic potential.
A proteomics approach with detection on western blots using an S-peptide tagged pan-tNOX (ENOX2) recombinant (scFv) antibody followed by alkaline phosphatase-linked anti S has revealed a family of more than 20 ENOX2 isoforms of varying molecular weights (34 to 94 kDa) and mostly of low isoelectric points (4.6 +/- 0.7) based on serum analysis. Different isoforms characterize cancers of different tissue origins indicative of both cancer presence and tissue site of origin. ENOX2 proteins are cancer-associated and differ from constitutive (CNOX or ENOX1) proteins primarily by the absence of a drug binding site to which the cancer-specific scFv is directed. All are located on the cell surface where they function both as terminal oxidases for plasma membrane electron transport and carry out protein disulfide-thiol interchange. These proteins are shed into the blood and can also be found in urine. The tNOX isoform technology is under development as a clinical aid to identify unknown or uncertain primary cancers, evaluation of metastatic spread in post surgery patients, monitoring remission following cessation of therapy and for early diagnosis in at-risk populations.
Morré
D James
DJ
Department of Medicinal Chemistry and Molecular Pharmacology, HANS Life Sciences Research Building, Purdue University, West Lafayette, IN 47907-2064,, USA. dj morre@yahoo.com
Hostetler
Brandon
B
Weston
Nicole
N
Kim
Chinpal
C
Morré
Dorothy M
DM
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000401:mortality; D011471:Prostatic Neoplasms / Q000378:metabolism; D020033:Protein Isoforms / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms
D020033:Protein Isoforms; D009247:NADH, NADPH Oxidoreductases; C431909:tumor-associated NADH oxidase