DACHSUND--able to revert cancerous cells to normal and predict bc prognosis!

[Lani]

The group used microarray technology - silicon chips containing ordered selections of genetic material upon which sample material can be tested - to analyze Dachshund expression during the development of breast cancer. The scientists compared normal breast cells, pre-cancerous "in situ" cells and more than 2,100 breast cancer cell samples. Dachshund gene expression was "significantly reduced" in breast cancer.

The average survival was almost 40 months better in women in whom their breast cancer continued to express Dachshund.

Dr. Pestell notes that the expression of Dachshund correlates with tumor size, stage and metastasis, with its expression greatly reduced in metastatic breast cancer cells. Dr. Pestell's team is examining other cell fate-determining genes in an attempt to identify new therapeutics for breast cancer and metastasis.


ABSTRACT: DACH1 Is a Cell Fate Determination Factor That Inhibits Cyclin D1 and Breast Tumor Growth [Molecular and Cellular Biology; Subscribe]
Obstacles to the expansion of cells with proliferative potential include the induction of cell death, telomere-based senescence, and the pRb and p53 tumor suppressors. Not infrequently, the molecular pathways regulating oncogenesis recapitulate aberrations of processes governing embryogenesis. The genetic network, consisting of the dachshund (dac), eyes absent (eya), eyeless, and sine oculis (so) genes, regulates cell fate determination in metazoans, with dac serving as a cointegrator through a So DNA-binding factor. Here, DACH1 inhibited oncogene-mediated breast oncogenesis, blocking breast cancer epithelial cell DNA synthesis, colony formation, growth in Matrigel, and tumor growth in mice. Genetic deletion studies demonstrated a requirement for cyclin D1 in DACH1-mediated inhibition of DNA synthesis. DACH1 repressed cyclin D1 through a novel mechanism via a c-Jun DNA-binding partner, requiring the DACH1 -helical DS domain which recruits corepressors to the local chromatin. Analysis of over 2,000 patients demonstrated increased nuclear DACH1 expression correlated inversely with cellular mitosis and predicted improved breast cancer patient survival. The cell fate determination factor, DACH1, arrests breast tumor proliferation and growth in vivo providing a new mechanistic and potential therapeutic insight into this common disease.

[Tom]

Wow Lani,

Just when I always think we have seen the best, another article blows us out of the water. What a novel approach. "If you can't make the kid play ball any better, then send him over to the other team".

This is great stuff. Imagine not losing any body tissue to grotesque surgery and radiation, but making them divide again and differentiate they way they used to before they went nuts!

I have to say I'm proud as a new daddy that our hometown has come up with this important research. Jefferson hospital has burned a place in my mind, as I slept on a windowsill there in my Dad's room for three months as he was consumed by his recurrent colorectal cancer. I can now say that I have a little better feeling about the place. Sounds silly, but those months took a lot out of my respect for the practice of medicine in this country. I hope they continue to be hard chargers to irradicate this source of pain and anguish for so many decent people. Let's get this thing solved in this decade. I know are brightest people have the talent.

Tom