Impaired binding of insulin to erythrocyte membrane receptor and the activation of nitric oxide synthase by the hormone in human breast cancer

Abstract

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.

The role of insulin dependent NO synthesis in the impaired production of maspin in human breast cancer

“…The decrease of cell surface insulin receptor number is not unique for neutrophils in breast cancer. We have reported before that the hormone receptor numbers in nonmalignant erythrocytes are also markedly decreased in this condition (Chakraborty et al 2004). As such it is possible that the decrease of insulin receptor number in the cell surface is a manifestation of systemic flaw in the receptor protein synthesis in general in breast cancer.…”

“…Since the synthesis of NO was found to be related to the binding of hormone to the receptor (Chakraborty et al 2004), we attempted to restore the impaired maspin production in malignant breast tissue and neutrophils from breast cancer patients through increased synthesis of NO by increasing the binding of insulin to these tissues in the presence of PGE 1 . We report herein that the treatment of these tissues from breast cancer with insulin in the presence of PGE 1 , in the assay mixture together with insulin resulted in partial restoration of NO synthesis that effected a partial restoration of the impaired synthesis of maspin in these tissues in breast cancer.…”

“…For example while excess NO can act as a procarcinogenic compound (Iwarkiri et al 2002), the physiological amounts of the same compound can act as a systemic anticancer agent (Kilbourn and Belloni 1990;Sinha et al 2002). We have recently reported that the binding of insulin to its highaffinity receptors on erythrocyte membrane in human breast cancer was impaired which resulted in the impaired synthesis of NO (Chakraborty et al 2004). The stimulated synthesis of NO in the purified membrane preparation by insulin was found to be related to the activation of a constitutive form of NOS by the hormone.…”