Reduced expression of endothelial and inducible nitric oxide synthase in a human breast cancer cell line which has acquired estrogen independence.
We have recently reported the presence of inducible nitric oxide synthase (iNOS) in the human breast cancer cell line ZR-75-1. The purpose of the present study was to examine differences in expression of endothelial (eNOS) and inducible nitric oxide synthase in normal human mammary epithelial cells (HMEC) compared with two variants of the ZR-75-1 cell line. One variant has acquired estrogen independence, the other has acquired resistance to tamoxifen. Immunohistochemical investigations demonstrated that 100% of HMEC cells staining positive for both eNOS and iNOS. ZR-75-1 cells showed 100% staining for eNOS and 52% positive staining for iNOS. There was no difference in staining between the parent cell line and cells which had acquired resistance to tamoxifen (ZR-75-9a1). However, in the breast cancer cell line which had acquired estrogen independence (ZR-PR-LT), less than 5% of cells exhibited positive staining for eNOS and staining for iNOS was undetectable. L-Arginine increased NO production in both ZR-75-9a1 and ZR-PR-LT cells. Progesterone was able to down regulate NO production in both ZR-75-1 and ZR-75-9a1 cells and this effect was reversible by RU486. These results support the suggestion that loss of NOS expression may be associated with the progression of breast cancers.
Martin
J H
JH
Division of Biomedical Sciences, University of Wolverhampton, UK.
Alalami
O
O
van den Berg
H W
HW
D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002417:Cattle; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015735:Mifepristone / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D011374:Progesterone / Q000494:pharmacology; D011817:Rabbits; D013629:Tamoxifen / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004967:Estrogens; D013629:Tamoxifen; D009569:Nitric Oxide; D015735:Mifepristone; D011374:Progesterone; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D013755:Tetradecanoylphorbol Acetate; D019331:NG-Nitroarginine Methyl Ester