Shpilberg Yaniv, Connor Michael K, Riddell Michael C
Horm Mol Biol Clin Investig. 2015 May;22(2):91-100. doi: 10.1515/hmbci-2015-0003.
Breast cancer is the second leading cause of cancer-related mortality in women. Glucocorticoids (GCs) have the potential to directly affect breast cancer or indirectly via changes to the tumor growth microenvironment a breast cancer is exposed to. The role of GCs in breast cancer progression by direct and indirect means are not fully understood.
To study the direct and indirect effects of GCs on breast cancer cell cycle regulation.
MCF7 breast cancer cells were incubated with increasing concentrations of corticosterone (CORT) to investigate the direct effects. In addition, MCF7 cells were cultured in conditioned media (CM) from primary adipose tissue excised from CORT-supplemented lean and obese male rats.
CORT alone resulted in dose-dependent increases in p27 and hypophosphorylated retinoblastoma protein (Rb) which was accompanied by a reduction in the number of cells in S-phase. CM prepared from adipose tissue overrode these direct CORT effects, suggesting that the tumor growth microenvironment created in the CM dominates MCF7 cell cycle regulation.
The direct inhibitory effects of CORT on cancer cell cycle progression are largely limited by the hormone's effects on adipose tissue biology.
乳腺癌是女性癌症相关死亡的第二大主要原因。糖皮质激素（GCs）有可能直接影响乳腺癌，或通过改变乳腺癌所暴露的肿瘤生长微环境间接产生影响。糖皮质激素通过直接和间接方式在乳腺癌进展中的作用尚未完全明确。
研究糖皮质激素对乳腺癌细胞周期调控的直接和间接影响。
用浓度递增的皮质酮（CORT）处理MCF7乳腺癌细胞，以研究其直接作用。此外，将MCF7细胞培养于从补充了CORT的瘦型和肥胖型雄性大鼠切除的原代脂肪组织的条件培养基（CM）中。
单独使用CORT导致p27和低磷酸化视网膜母细胞瘤蛋白（Rb）呈剂量依赖性增加，同时伴有S期细胞数量减少。由脂肪组织制备的CM抵消了这些CORT的直接作用，表明CM中产生的肿瘤生长微环境主导了MCF7细胞周期调控。
CORT对癌细胞周期进展的直接抑制作用在很大程度上受该激素对脂肪组织生物学作用的限制。
