The role of insulin dependent NO synthesis in the impaired production of maspin in human breast cancer.
OBJECTIVE
The synthesis of maspin, a protein with various anti-breast cancer properties has been reported to be produced in normal breast tissue but not in breast cancer cells. We investigated the role of insulin receptors and their upregulation by prostaglandin E(1) in vitro for the stimulation of NO synthesis by the hormone, and its consequence on maspin production in normal neutrophils and malignant cells in breast cancer.


METHODS
Maspin and NO were determined by ELISA and methemoglobin method, respectively.


RESULTS
The treatment of neutrophils and malignant breast cancer cells with prostaglandin E(1) resulted in partial restoration of the impaired receptor numbers, and resulted in partial normalization of NO and maspin production in these cells compared to normal counterparts. It was not feasible to stimulate NO synthesis to normal ranges by the upregulation of receptor number due to intrinsic decrease of insulin receptors in breast cancer cells. However, aspirin, which was found to stimulate NO synthesis to normal ranges, normalized maspin production in these cells in breast cancer.


CONCLUSIONS
The impaired maspin production was found to be the consequence of impaired insulin induced NO production in breast cancer due to the decrease of insulin receptor binding. Restoration of NO production by aspirin can be useful for the restoration of maspin production in breast cancer.
Sinha Institute of Medical Science and Technology, 288 Kendua Main Road, Garia, 700084, Calcutta, India.
G V
GV
Girish
G
G
Bhattacharya
A Kumar
AK
Sinha
D000368:Aged; D000527:Alprostadil / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism; D012680:Sensitivity and Specificity; D015843:Serpins / Q000096:biosynthesis*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
D007328:Insulin; C085344:SERPIN-B5; D015843:Serpins; D009569:Nitric Oxide; D011972:Receptor, Insulin; D000527:Alprostadil; D006152:Cyclic GMP; D001241:Aspirin