first there was Tiptoe, now there is Dachsund!!

[Lani]

: Proc Natl Acad Sci U S A. 2008 May 8 [Epub ahead of print]

Dachshund inhibits oncogene-induced breast cancer cellular migration and invasion through suppression of interleukin-8.

Wu K, Katiyar S, Li A, Liu M, Ju X, Popov VM, Jiao X, Lisanti MP, Casola A, Pestell RG.
Departments of Cancer Biology and.
Oncogene-mediated signaling to the host environment induces a subset of cytokines and chemokines. The Drosophila Dac gene promotes migration of the morphogenetic furrow during eye development. Expression of the cell-fate determination factor Dachshund (DACH1) was lost in poor prognosis invasive breast cancer. Mouse embryo fibroblasts derived from Dach1(-/-) mice demonstrated endogenous Dach1 constitutively represses cellular migration. DACH1 inhibited cellular migration and invasion of oncogene (Ras, Myc, ErbB2, c-Raf)-transformed human breast epithelial cells. An unbiased proteomic analysis identified and immunoneutralizing antibody and reconstitution experiments demonstrated IL-8 is a critical target of DACH1 mediating breast cancer cellular migration and metastasis in vivo. DACH1 bound the endogenous IL-8 promoter in ChIP assays and repressed the IL-8 promoter through the AP-1 and NF-kappaB binding sites. Collectively, our data identify a pathway by which an endogenous cell-fate determination factor blocks oncogene-dependent tumor metastasis via a key heterotypic mediator.

[StephN]

HUH? I must have had too much wine tonight with the ribs.
But on second reading I am NOT seeing things.
Still don't quite understand ....

[donocco5w4]

Interleukin 8 is one of many cyokines. apparently it is necessary or involved in the metastasis of breast cancer cells. apparently this Dasch gene protein inhibits metastasis by inhibiting the action of interleukin 8 when it is functioning properly.

It would be quite possible to develop a monoclonal antibody to inhibit interleukin 8 and help slow down metastasis. Avastin is a monoclonal antibody that inhibits Vascular Endothelial Growth Factor. Herceptin is a monoclonal antibody that in hibits the Her2Neu protein. Tocilizumab is a monoclonal antibody being developed against Interleukin 6 and is to be used to treat severe Rheumatoid Arthritis.Interleukin 6 is very involved in the cancer known as Multiple Myeloma so theoretically Tocilizumab might be valable in this disease too.

This new info about Dasch and Interlekin 8 opens p a new area to target. NF Kappa beta is also mentioned. Stimulation of NFKappa beta causes Interleukin 6 release and apparently the Dasch gene also inhibits this target also. In fact when NFKappa b is activated a large number of "pro-cancer" (for lack of a better word) chemicals are activated. I know as a pharmacist that NSAID drgs like Aspirin and Celebrex inhibit NFKappa b also and could be used in combination with this antibody against Interleukin 8, when it is developed.

Paul

[R.B.]

And excess Omega six promotes higher levels of IL6.

RB

[PinkGirl]

I figured it out StephN. Lani is talking about making a monoclonal antibody out of the ovaries of weiner dogs. ;)

[StephN]

Better NOT tell my daughter or my niece sinch they both have long-haired mini Dachs...
Close your long floppy ears Tootsie and Miloo.

Thanks for the lay-speak.
I heard about dozens of new targets being worked on when we were at San Diego, so this actually does not surprise me that much.

[RhondaH]

miniature short hair dashchund that HE is a boy...WHEW, lucky Oscar.

Rhonda

[hutchibk]

Wish I had known - as we had over 500 wiener-dogs competing at the world famous Buda, Texas Wiener Dog Races last weekend (2 blocks from my house)... I coulda done some "harvesting" LOL.