Antiproliferative and apoptotic effect of TGF-β 1 in bovine mammary epithelial BME-UV1 cells

• Published in: Comparative biochemistry and physiology. Toxicology & pharmacology 2003-04, Vol.134 (4), p.417-430
• Main Authors: Kolek, O., Gajkowska, B., Godlewski, M.M., Motyl, T.
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Bax; Bovine mammary epithelial BME-UV1 cells; Caspase-3; Cattle; Cell Line; Epithelial Cells - drug effects; Epithelial Cells - physiology; Female; Growth Inhibitors - pharmacology; Growth Inhibitors - physiology; Laser scanning cytometry; m-Calpain; Mammary Glands, Animal - drug effects; Mammary Glands, Animal - metabolism; TGF-β 1; Transforming Growth Factor beta - pharmacology; Transforming Growth Factor beta - physiology; Transforming Growth Factor beta1; VDAC-1
• ISSN: 1532-0456; 1878-1659
• DOI: 10.1016/S1532-0456(02)00249-1

Transforming growth factor β1 (TGF-β 1) is regarded as an important auto/paracrine regulator of mammary gland involution, however, its apoptotic effect and inhibition of growth in bovine mammary epithelial cells (MEC) has not been documented. In the present study, laser scanning cytometry, confocal and immunoelectron microscopy techniques were used for quantitative and qualitative analyzes of apoptosis, cell cycle and expression, subcellular redistribution and interactions of apoptosis-related proteins in bovine BME-UV1 MEC exposed to TGF-β 1. TGF-β 1 exerted both antiproliferative and apoptotic action. The antiproliferative effect was manifested by increase of cell number in G1 phase with simultaneous decrease of cell number in S and G2/M phases. It resulted in significant increase of G1/S ratio in TGF-β 1 treated cells, indicating partial cell cycle arrest at the G1–S transition. Apoptosis induced by TGF-β 1 manifested by characteristic morphological changes. Among biochemical features of TGF-β 1-induced apoptosis in BME-UV1 cells we found: (1) an increase of cell number with lowered DNA content and condensed chromatin, (2) enhanced expression of caspase-3 and m-calpain, (3) elevated number of 89 kDa PARP degradation fragments, and (4) aggregation of Bax and its interactions with voltage dependant anion channel-1. In conclusion, antiproliferative and apoptotic action of TGF-β 1, observed in the culture of BME-UV1 cells, suggests an essential role of this cytokine in the regulation of mammary gland involution in cow.