Impaired binding of insulin to erythrocyte membrane receptor and the activation of nitric oxide synthase by the hormone in human breast cancer.
OBJECTIVE
Nitric oxide, a messenger molecule has been reported as having various antineoplastic properties. The activation of insulin-activated nitric oxide synthase (IANOS) was found to be related to the production of NO as a result of the binding of insulin to its receptor through the activation of tyrosine kinase in erythrocyte membrane. As nitric oxide is reported to be a systemic anticancer agent, studies were carried out to determine the role of insulin receptor binding that lead to the activation of tyrosine kinase and IANOS in erythrocytes in breast cancer.


METHODS
Blood samples were collected from female breast cancer patients who, at the time of participation in the study, had not undergone any therapeutic intervention but had opted for surgery. The binding of insulin to its receptor in erythrocyte membrane and the activation of both receptor tyrosine kinase and IANOS due to the hormone binding were determined and compared with the appropriate control.


RESULTS
It was found that the impaired NO synthesis in erythrocyte membrane in breast cancer was related to the marked decrease of insulin binding sites of the high-affinity hormone receptor population. This impaired insulin binding to high-affinity receptors resulted in the impairment of both reaction velocity (Vmax) of the IANOS and receptor tyrosine kinase activation.


CONCLUSIONS
These results indicated that the impairment of interaction between insulin and its high-affinity receptors in erythrocyte membrane might be a critical pathophysiological event in the development of breast cancer.
Sinha Institute of Medical Science and Technology, 288 Kendua Main Road, 700 084, Garia, Calcutta, India.
S
S
Chakraborty
G V
GV
Girish
A K
AK
Sinha
D000328:Adult; D001943:Breast Neoplasms / Q000201:enzymology*; D016022:Case-Control Studies; D004789:Enzyme Activation; D004910:Erythrocyte Membrane / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism*
D007328:Insulin; D019001:Nitric Oxide Synthase; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin