- Tytuł:
- Side-chain modified vitamin D analogs require activation of both PI 3-K and erk1,2 signal transduction pathways to induce differentiation of human promyelocytic leukemia cells.
- Autorzy:
-
Marcinkowska, Ewa
Kutner, Andrzej - Powiązania:
- https://bibliotekanauki.pl/articles/1043768.pdf
- Data publikacji:
- 2002
- Wydawca:
- Polskie Towarzystwo Biochemiczne
- Tematy:
-
CD11b
cytosolic phospholipase A2
p70S6K
nuclear vitamin D receptor
CD14
analogs
phosphatidylinositol 3-kinase
extracellular-signal regulated kinase
1,25-dihydroxyvitamin D3
HL-60 cells
differentiation - Opis:
- Synthetic analogs of vitamin D for potential use in differentiation therapy should selectively regulate genes necessary for differentiation without inducing any perturbations in calcium homeostasis. PRI-1906, an analog of vitamin D2, and PRI-2191, an analog of vitamin D3 bind nuclear vitamin D receptor (nVDR) with substantially lower affinity than 1,25-dihydroxyvitamin D3 (1,25-D3), but have higher differentiation-inducing activity as estimated in HL-60 leukemia cell model. To examine how their increased differentiation-inducing activity is regulated we tested the hypothesis that membrane-mediated events, unrelated to nVDR, take part in the differentiation in response to PRI-1906 and PRI-2191. The induction of leukemia cell differentiation in response to the analogs of vitamin D was inhibited by LY294002 (phosphatidylinositol 3-kinase inhibitor), PD98059 (inhibitor of MEK1,2, an upstream regulator of extracellular-signal regulated kinase) and rapamycin (p70S6K inhibitor) pointing out that activation of signal transduction pathways unrelated to nVDR is necessary for differentiation. On the other hand, inhibition of cytosolic phospholipase A2 accelerated the differentiation of HL-60 cells induced by either 1,25-D3 or by the vitamin D analogs suggesting possible existence of a feedback loop between extracellular-signal regulated kinases and phospholipase A2.
- Źródło:
-
Acta Biochimica Polonica; 2002, 49, 2; 393-406
0001-527X - Pojawia się w:
- Acta Biochimica Polonica
- Dostawca treści:
- Biblioteka Nauki
Artykuł