Carcinogenesis Advance Access published online on November 5, 2005
Carcinogenesis, doi:10.1093/carcin/bgi250
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1 Servicio de Análisis Clínicos, University Hospital Virgen de la Arrixaca, Ctra. Madrid-Cartagena s/n, El Palmar, E-30120, Murcia, Spain; Departamento de Bioquímica y Biología Molecular-A, Facultad de Biología, Universidad de Murcia, Spain
* To whom correspondence should be addressed. The probable involvement of acetyl- (AChE) and butyrylcholinesterase (BChE) in cancer and the relevance of cholinergic responses for lung cancer growth prompted us to study whether cholinesterase activity of human lung is altered by malignancy. Surgical pieces of non-small lung carcinomas (NSLC) and their adjacent non-cancerous tissues (ANCT) were analyzed for AChE and BChE activities. AChE activity in AC was 7.80 ± 5.59 nmol of substrate hydrolyzed per min and per mg of protein (mU/mg), the same as in their ANCT (8.83 ± 4.72 mU/mg; p=0.823); in LCC, 7.52 ± 3.32 mU/mg, nearly 50% less than in their ANCT (15.39 ± 5.66 mU/mg; p=0.043); and in SCC, 1.39 ± 0.58 mU/mg, 80% less than in ANCT (6.08 ± 2.88 mU/mg; p=0.003). BChE activity was 5.85 ± 3.20 mU/mg in AC and 9.56 ± 3.38 mU/mg in ANCT (p=0.022); 2.94 ± 2.01 mU/mg in LCC and 6.50 ± 6.63 mU/mg in ANCT (p=0.068); and 4.49 ± 2.30 mU/mg in SCC and ANCT 6.56 ± 4.09 mU/mg (p=0.026). Abundant AChE dimers and fewer monomers were identified in lung and, although their distribution was unaffected by cancer, the binding with concanavalin A revealed changes in AChE glycosylation between SCC and their ANCT. The fall in BChE activity affected all molecules, with a strong decrease of the amphiphilic tetramers. Western blotting revealed protein bands with the expected mass of the principal AChE subunits, and the deeper intensity of the protein signal in SCC than in healthy lung, in lanes loaded with the same units of AChE activity, supported an augment in the amount of AChE protein/unit of AChE activity in SCC. The increased availability of ACh in neoplastic lung, resulting from the fall of ChE activity, may enhance cholinergic signalling and contribute to tumour progression.
Received May 12, 2005
Revised October 3, 2005
Accepted October 26, 2005
CANCER BIOLOGY
Cholinesterase activity of human lung tumours varies according to their histological classification
2 Servicio de Análisis Clínicos, University Hospital Virgen de la Arrixaca, Ctra. Madrid-Cartagena s/n, El Palmar, E-30120, Murcia, Spain
3 Cirugía Torácica, University Hospital Virgen de la Arrixaca, Ctra. Madrid-Cartagena s/n, El Palmar, E-30120, Murcia, Spain
4 Departamento de Bioquímica y Biología Molecular-A, Facultad de Biología, Universidad de Murcia, Spain
Juan Cabezas-Herrera, E-mail: juan.cabezas{at}carm.es
Abstract
¶Both authors have contributed equally to this work.
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