Syk Protective Against Breast Cancer

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Inhibitors of the non-receptor spleen tyrosine kinase (Syk) are being developed to treat a variety of allergic and autoimmune disorders, as well as some types of cancer, but researchers at Georgetown University Medical Center have cautioned that Syk controls the growth of normal breast cells and prevents the development of breast cancer.

Although it is not known what causes loss of Syk function, Syk is negatively correlated with invasion and metastasis of tumour cells and, as breast tumours progress, more and more Syk protein is lost. Since total knock-out of Syk is perinatally lethal, the researchers created mice with only one copy of the gene and found that loss of the single allele led to increased proliferation and invasion of normal breast cells in the mouse mammary gland during puberty, and resulted in development of breast cancer in adulthood.

Three colour confocal images of cells cultured on crosslinked gelatin showing the distribution of DAPI (nuclei, blue), phalloidin (F-act, green), and vimentin (magenta) in control (left) versus Syk siRNA transfected MCF10A cells (right). Scale bars = 20 µm. Image: PLoSone
Three colour confocal images of cells cultured on crosslinked gelatin showing the distribution of DAPI (nuclei, blue), phalloidin (F-act, green), and vimentin (magenta) in control (left) versus Syk siRNA transfected MCF10A cells (right). Scale bars = 20 µm.

Image: PLoSone


siRNA or shRNA knockdown of Syk protein in cultures of normal human breast epithelial cells also dramatically increased proliferation and invasion. Syk loss was shown to release inhibition of a number of signalling pathways that are normally repressed in epithelial cells and that promote increased proliferation, motility, and invasiveness. The findings, which were published on October 15th in the journal PLoS ONE, suggest that Syk plays an important role in controlling growth as breast tissue develops and acts as a tumour suppressor for breast cancer. The finding that only partial loss of Syk function in mice was sufficient to induce mammary carcinomas underscores the potential risk of Syk inhibition in promoting breast cancer. The team hope that identification of the pathways that are negatively regulated by Syk will ultimately provide new targets for the treatment of breast cancer.

2 thoughts on “Syk Protective Against Breast Cancer”

  1. I just read about a new targeted cancer drug that has been shown to shrink tumors in women with metastatic breast cancer after an average of seven other drugs, including Herceptin, failed. The new drug, called T-DM1, combines Herceptin with a potent chemotherapy drug. Here’s to keeping our hopes alive that someday this retched disease can be nothing but a memory! One word comes to mind when it comes to breast cancer conquer. Happy Holidays to All!

  2. I am not well versed (as I am a synthetic organic chemist and interested in understanding about the antisense drugs, RNAis & other nucleic acid derivatives) with mode of action, I found this paper interesting and I am copying here the summary of the paper for your reference pls. do comment…

    “Short hairpin RNAs (shRNAs) capable of stably suppressing gene function by RNA interference (RNAi) can mimic tumor-suppressor-gene loss in mice. By selecting for shRNAs capable of accelerating lymphomagenesis in a well-characterized mouse lymphoma model, we identified over ten candidate tumor suppressors, including Sfrp1, Numb, Mek1, and Angiopoietin 2. Several components of the DNA damage response machinery were also identified, including Rad17, which acts as a haploinsufficient tumor suppressor that responds to oncogenic stress and whose loss is associated with poor prognosis in human patients”.

    Functional Identification of Tumor-Suppressor Genes through an In Vivo RNA Interference Screen in a Mouse Lymphoma Model
    Scott W. Lowe et. al.,

    Journal : http://www.sciencedirect.com

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