SRSF3 and hnRNP H1 regulate a splicing hotspot of HER2 in breast cancer cells.

Overexpression of the oncogene HER2 occurs in 20-30% of invasive breast cancer and is associated with poor prognosis. A number of different splice variants of HER2 have been identified which produce functionally different proteins. Previously these splice variants have been investigated separately, but in the present study we collectively look at the expression and regulation of a group of HER2 splice variants produced by a splicing hotspot.

The HER2 Signaling Network in Breast Cancer--Like a Spider in its Web.

The human epidermal growth factor receptor 2 (HER2) is a major player in the survival and proliferation of tumour cells and is overexpressed in up to 30 % of breast cancer cases. A considerable amount of work has been undertaken to unravel the activity and function of HER2 to try and develop effective therapies that impede its action in HER2 positive breast tumours. Research has focused on exploring the HER2 activated phosphoinositide-3-kinase (PI3K)/AKT and rat sarcoma/mitogen-activated protein kinase (RAS/MAPK) pathways for therapies.

Breast cancer metastasis: demonstration that FOXP3 regulates CXCR4 expression and the response to CXCL12.

The X-linked transcription factor FOXP3 is expressed by epithelial cells of organs including the breast, where it is considered a tumour suppressor. The chemokine receptor CXCR4 also regulates the development of breast cancer by stimulating cell migration towards CXCL12-expressing sites of metastatic spread. During activation, human T cells show reciprocal regulation of FOXP3 and CXCR4.

Clinical Significance of HER-2 Splice Variants in Breast Cancer Progression and Drug Resistance.

Overexpression of human epidermal growth factor receptor (HER-2) occurs in 20-30% of breast cancers and confers survival and proliferative advantages on the tumour cells making HER-2 an ideal therapeutic target for drugs like Herceptin. Continued delineation of tumour biology has identified splice variants of HER-2, with contrasting roles in tumour cell biology. For example, the splice variant Δ16HER-2 (results from exon 16 skipping) increases transformation of cancer cells and is associated with treatment resistance; conversely, Herstatin (results from intron 8 retention) and p100 (results from intron 15 retention) inhibit tumour cell proliferation.

The role of FOXP3 in the development and metastatic spread of breast cancer.

The transcription factor FOXP3 is widely known for its role in the development and function of immunoregulatory T cells. However, it has been discovered recently that FOXP3 is also expressed in epithelial cells of the normal human breast, ovary and prostate. Aggressive cancer of these epithelial tissues often correlates with abnormal expression of FOXP3, which can be either absent or underexpressed at transcript or protein levels.