* Cyclic AMP regulates the migration and invasion potential of human pancreatic cancer cells.
- Aggressive dissemination and metastasis of pancreatic ductal adenocarcinoma (PDAC) results in poor prognosis and marked lethality. Rho monomeric G protein levels are increased in pancreatic cancer tissue. As the mechanisms underlying PDAC malignancy are little understood, we investigated the role for cAMP in regulating monomeric G protein regulated invasion and migration of pancreatic cancer cells. Treatment of PDAC cells with cAMP elevating agents that activate adenylyl cyclases, forskolin, protein kinase A (PKA), 6-Bnz-cAMP, or the cyclic nucleotide phosphodiesterase inhibitor cilostamide significantly decreased migration and Matrigel invasion of PDAC cell lines. Inhibition was dose-dependent and not significantly different between forskolin or cilostamide treatment. cAMP elevating drugs not only blocked basal migration, but similarly abrogated transforming-growth factor-β-directed PDAC cell migration and invasion. The inhibitory effects of cAMP were prevented by the pharmacological blockade of PKA. Drugs that increase cellular cAMP levels decreased levels of active RhoA or RhoC, with a concomitant increase in phosphorylated RhoA. Diminished Rho signaling was correlated with the appearance of thickened cortical actin bands along the perimeter of non-motile forskolin or cilostamide-treated cells. Decreased migration did not reflect alterations in cell growth or programmed cell death. Collectively these data support the notion that increased levels of cAMP specifically hinder PDAC cell motility through F-actin remodeling.
=>直通の, のために, の間じゅう, 終わって, を貫いて, の中を通って, のいたるところに, を通じて
Overview of adj through
The adj through has 2 senses (first 1 from tagged texts)
1. (4) done, through, through with -- (having finished or arrived at completion; "certain to make
history before he's done"; "it's a done deed"; "after the treatment, the patient is through except
for follow-up"; "almost through with his studies")
2. through -- ((of a route or journey etc.) continuing without requiring stops or changes; "a
through street"; "a through bus"; "through traffic")
Overview of adv through
The adv through has 5 senses (first 3 from tagged texts)
1. (5) through -- (from beginning to end; "read this book through")
2. (2) through -- (over the whole distance; "this bus goes through to New York")
3. (1) through -- (to completion; "think this through very carefully!")
4. through -- (in diameter; "this cylinder measures 15 inches through")
5. through, through and through -- (throughout the entire extent; "got soaked through in the rain";
"I'm frozen through"; "a letter shot through with the writer's personality"; "knew him through and
through"; "boards rotten through and through")
--- WordNet end ---