Dissimilar effects of LY 294002 and PD 098059 in IGF-I- mediated inhibition of TGF-beta1 expression and apoptosis in bovine mammary epithelial cells

• Autorzy: Zarzynska J. , Motyl T.
• Języki publikacji: EN

Abstrakty

EN

In mammary epithelial cells (MEC) TGF-ß1 is the auto-/paracrine growth inhibitor and inducer of apoptosis and therefore is considered as an important local regulator of mammary tissue involution. However, the mechanisms of controlled TGF-ß1 expression in the course of bovine mammary gland remodelling are still unclear. Recent study performed in this laboratory support the evidence that TGF-ß1 expression in bovine MEC is regulated by hormones of somatotropic axis (GH, IGF-I and somatostatin). Present study was focused on the contribution of IGF-I-induced signaling pathways in anti-TGF-ß1 and anti-apoptotic effects of IGF-I. Laser scanning cytometry was applied for the measurement of TGF-ß1 content and apoptotic cell number in bovine BME-UV1 MEC. Involution of the bovine mammary gland in vitro was modeled by decreasing the availability of FBS for bovine MEC. Reducing FBS content in the medium from 10% to 0.5% evoked highly significant increase of TGF-ß1 expression and increase of apoptotic cell number. IGF-I (50 ng/ml) completely abrogated FBS deficiency-induced TGF-ß1 expression and apoptosis in bovine MEC. In order to establish which of the IGF-I signaling pathways contributed to anti-TGF-ß1 and anti-apoptotic effects, the inhibitors of PI3-kinase - (LY 294002) and MEK- (MAPKK for ERK) (PD 098059) mediated signaling pathways were applied to our model. The results clearly showed that inhibition of PI3-K reverses the ability of IGF-I to suppress TGF-ß1 expression and apoptosis. An inhibition of ERK1/2 pathway even potentiated inhibitory effect of IGF-I on TGF-ß1 expression, but partially abrogated anti-apoptotic effect of IGF-I. In conclusion, the results of the study indicate that PI3-K/Akt pathway contributed significantly to the inhibition of TGF-ß1 expression by IGF-I, whereas both PI3-K/Akt and ERK1/2 pathways are involved in the anti-apoptotic effect of IGF-I in bovine MEC.

Słowa kluczowe

EN

mammary epithelial cell; transforming growth factor-beta 1; somatotropic axis; somatotrophic zob.somatotropic; apoptosis; laser scanning cytometry; mammary tissue

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology. Supplement
• Rocznik: 2005
• Tom: 56
• Numer: 3
• Opis fizyczny: p.181-193,fig.,ref.

Twórcy

autor

Zarzynska J.

• Warsaw Agricultural University, Nowoursynowska 159, 02-787 Warsaw, Poland

autor

Motyl T.