Cooperativity between the polyamine pathway and HER‐2neu in transformation of human mammary epithelial cells in culture: Role of the MAPK pathway

Manni, Andrea; Wechter, Rita; Verderame, Michael F.; Mauger, David T.

doi:10.1002/(sici)1097-0215(19980518)76:4<563::aid-ijc20>3.3.co;2-t

Cited by 1 publication

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another class of molecules correlated to both cell growth and cell death is represented by polyamines [9,10], and actually, evidence indicates a cross‐talk between these organic polycations and the MAPK pathway [11–13]. Polyamines are absolutely required for cell proliferation, and the inhibition of their biosynthesis represents a pharmacological tool in cell growth control [9].…”

Section: Introductionmentioning

confidence: 99%

Caspase activation in etoposide‐treated fibroblasts is correlated to ERK phosphorylation and both events are blocked by polyamine depletion

et al. 2002

View full text Add to dashboard Cite

Activation of the extracellular signal-regulated kinases (ERKs) 1 and 2 is correlated to cell survival, but in some cases ERKs can act in signal transduction pathways leading to apoptosis. Treatment of mouse ¢broblasts with 20 W WM etoposide elicited a sustained phosphorylation of ERK 1/2, that increased until 24 h from the treatment in parallel with caspase activity. The inhibitor of ERK activation PD98059 abolished caspase activation, but caspase inhibition did not reduce ERK 1/2 phosphorylation, suggesting that ERK activation is placed upstream of caspases. Both ERK and caspase activation were blocked in cells depleted of polyamines by the ornithine decarboxylase inhibitor K K-di£uoromethylornithine (DFMO). In etoposide-treated cells, DFMO also abolished phosphorylation of c-Jun NH 2 -terminal kinases triggered by the drug. Polyamine replenishment with exogenous putrescine restored the ability of the cells to undergo caspase activation and ERK 1/2 phosphorylation in response to etoposide. Ornithine decarboxylase activity decreased after etoposide, indicating that DFMO exerts its e¡ect by depleting cellular polyamines before induction of apoptosis. These results reveal a role for polyamines in the transduction of the death signal triggered by etoposide. ß

show abstract

Section: Introductionmentioning

confidence: 99%