* p66Shc longevity protein regulates the proliferation of human ovarian cancer cells.
- p66Shc functions as a longevity protein in murine and exhibits oxidase activity in regulating diverse biological activities. In this study, we investigated the role of p66Shc protein in regulating ovarian cancer (OCa) cell proliferation. Among three cell lines examined, the slowest growing OVCAR-3 cells have the lowest level of p66Shc protein. Transient transfection with p66Shc cDNA expression vector in OVCAR-3 cells increases cell proliferation. Conversely, knock-down of p66Shc by shRNA in rapidly growing SKOV-3 cells results in decreased cell growth. In estrogen (E2)-treated CaOV-3 cells, elevated p66Shc protein level correlates with ROS level, ErbB-2 and ERK/MAPK activation, and cell proliferation. Further, the E2-stimulated proliferation of CaOV-3 cells was blocked by antioxidants and ErbB-2 inhibitor. Additionally, in E2-stimulated cells, the tartrate-sensitive, but not the tartrate-resistant, phosphatase activity decreases; concurrently, the tyrosine phosphorylation of ErbB-2 increases. Conversely, inhibition of phosphatase activity by L(+)-tartrate treatment increases p66Shc protein level, ErbB-2 tyrosine phosphorylation, ERK/MAPK activation, and cell growth. Further, inhibition of the ERK/MAPK pathway by PD98059 blocks E2-induced ERK/MAPK activation and cell proliferation in CaOV-3 cells. Moreover, immunohistochemical analyses showed that the p66Shc protein level was significantly higher in cancerous cells than in noncancerous cells in archival OCa tissues (n = 76; P = 0.00037). These data collectively indicate that p66Shc protein plays a critical role in up-regulating OCa progression.
=>1.さらにずっと, さらに先に, 一層遠く, その上, 更に, もっと遠い, なお一層の, さらに遠く,
もっと先に, いっそうはるかに, さらにまた, さらになお(furthermore), 2.進める, 助成する, 促進する
Overview of verb further
The verb further has 2 senses (first 2 from tagged texts)
1. (7) foster, further -- (promote the growth of; "Foster our children's well-being and education")
2. (2) promote, advance, boost, further, encourage -- (contribute to the progress or growth of; "I
am promoting the use of computers in the classroom")
Overview of adj further
The adj further has 1 sense (first 1 from tagged texts)
1. (2) further, farther -- (more distant in especially degree; "nothing could be further from the
truth"; "further from our expectations"; "farther from the truth"; "farther from our expectations")
Overview of adv further
The adv further has 3 senses (first 3 from tagged texts)
1. (33) further, farther -- (to or at a greater extent or degree or a more advanced stage (`further'
is used more often than `farther' in this abstract sense); "further complicated by uncertainty about
the future"; "let's not discuss it further"; "nothing could be further from the truth"; "they are
further along in their research than we expected"; "the application of the law was extended
farther"; "he is going no farther in his studies")
2. (10) further -- (in addition or furthermore; "if we further suppose"; "stated further that he
would not cooperate with them"; "they are definitely coming; further, they should be here already")
3. (1) farther, further -- (to or at a greater distance in time or space (`farther' is used more
frequently than `further' in this physical sense); "farther north"; "moved farther away"; "farther
down the corridor"; "the practice may go back still farther to the Druids"; "went only three miles
further"; "further in the future")
Overview of adv far
The adv far has 5 senses (first 4 from tagged texts)
1. (61) far -- (to a considerable degree; very much; "a far far better thing that I do"; "felt far
worse than yesterday"; "eyes far too close together")
2. (39) far -- (at or to or from a great distance in space; "he traveled far"; "strayed far from
home"; "sat far away from each other")
3. (22) far -- (at or to a certain point or degree; "I can only go so far before I have to give up";
"how far can we get with this kind of argument?")
4. (3) far -- (remote in time; "if we could see far into the future"; "all that happened far in the
past")
5. far -- (to an advanced stage or point; "a young man who will go very far")
--- WordNet end ---