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Updated: Dec 9, 2025
Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
Assessing the predictive response of a simple and sensitive blood-based biomarker between estrogen-negative solid
Srinidi Mohan1, Seema Patel1, David Barlow1
1Department of Pharmaceutical Sciences, College of Pharmacy, University of New England, Portland, ME, USA.
Purpose:
We investigated Nw-hydroxy l-Arginine (NOHA) predictive response in serous ovarian carcinoma based on estrogen-hormone receptor expression status; and assessed the distinctive NOHA response between estrogen-receptor-negative (ER-) tumor subtypes of ovarian and breast cancer.
Materials/Methods:
Three-dimensional (3D) spheroids models of ER- and estrogen-receptor-positive (ER+) from breast and ovarian tumor, cultured for 9 weeks, were assayed for cellular levels of inducible nitric oxide synthase (NOS2), nitric oxide (as total nitrite) and l-Arginine, and compared to NOHA in culture medium. Statistical difference was set at p < 0.01.
Results:
Nine-week in vitro studies showed a progressive NOHA reduction in culture medium by at least 0.4-0.8 fold, and 0.65-0.92 fold only in the ER- breast tumor and ER- ovarian tumor 3D spheroids, respectively; with increases in cellular NOS2 and nitric-oxide levels, by at least 1.0-2.45 fold in both ER- tumor subtype 3D spheroids (p < 0.01; n = 6). Within ER- subtypes, medium NOHA decreased by ≥ 38.9% in ovarian cancer over breast cancer 3D-spheroids, with cellular increases in NOS2 (by ≥ 17.4%), and nitric oxide (by ≥ 18.8%). Cellular l-Arginine to medium NOHA ratio was higher, and by at least 6.5-22.5 fold in ER- breast tumor 3D-spheroids, and at least 10-70 fold in ER- ovarian tumor 3D spheroids, than in ER+ and control conditions; and was ≥48% higher in ER- ovarian cancer than in ER- breast cancer 3D-spheroids.
Conclusions:
The present study shows NOHA as a sensitive and selective indicator differentiating and distinguishing ER- subtypes based on the tumor grade.
