New Target for Breast Cancer?

In the UK four out of five women who suffer from hormonal breast cancer are oestrogen positive which means that the receptor for oestrogen is overexpressed. Oestrogen is required for the proliferation and growth of breast cancer. Overexpressed oestrogen receptors are diagnosed in 50-80% of breast tumors cases. Recently researcher in UK found 3 new genes, C6ORF96, C6ORF97, and C6ORF211, located just upstream of the known oestrogen receptor gene ESR1. ESR1 is an important breast cancer biomarker oestrogen receptor. The 3 new genes have been shown to tightly co-expressed with ESR1 but behave separately from it. At the nucleotide level, all three ORFs show some homology with ESR1, indicating that they may have emerged from gene duplication events. This discovery is astonishing because ESR1 has been extensively studied and is located in one of the most heavily studied areas of the genome.

Further analysis revealed that the protein encoded by C6ORF211 was expressed mainly in the cytoplasm. C6ORF211 was shown to drive the growth of tumor. In a proteomic screen the protein has been found to interact with SAP18, a Sin3A-associated cell growth inhibiting protein. This reported interaction was hypothesized as one of the reasons that there was a suppression of proliferation in cultured cells where C6ORF211 was knocked down. Contrarily, a high level of activity of C6ORF97 predicted an improvement of “disease-free survival” in tamoxifen-treated dataset, independently from ESR1. The gene was a good predictor of response to tamoxifen. Less was known about C6ORF96, but it was being researched by the team.

Tamoxifen works by competitively blocking binding of oestrogen to receptors and therefore decreasing the transcriptional activation level of genes required for tumor growth. Tamoxifen is not shown to efficiently affect the activity of the new discovered genes, thus opening up a possible synergistic drug treatment for breast cancer along with the current treatment. Professor Mitch Dowsett, who lead the team at the Breakthrough Breast Cancer Research Centre at the ICR, added:

"This research is exciting because it shows that while the oestrogen receptor is the main driver of hormonal breast cancer, there are others next door to it that also appears to influence breast cancer behavior. We now need to better understand how they work together and how we can utilize them to save lives of women with breast cancer."

Hopefully the discovery of the new genes will help us to develop new drugs can cure breast cancer. The problem with the current treatment is that he tumors develop resistance overtime and may come back after the surgery and spread to another place. Perhaps with better and more advanced technologies, cancer can be treated as a curable disease.

Citation:

Scientist discover three genes link to breast cancer. Thursday, 5th May 2011. Mackenzie, Carla.
<http://www.figo.org/news/scientists-discover-three-genes-linked-breast-cancer-003612>
C6ORF211 Genes Catalyze the Growth of Tumor in Breast. Wednesday, 4th May 2011. Wilkins, Dave.
<http://topnews.us/content/239524-c6orf211-genes-catalyze-growth-tumor-breast>
Three gene discovery may lead to new breast cancer treatments. 4th May 2011. Kraft, Sy.
<http://www.medicalnewstoday.com/articles/224227.php>
Oestrogen receptors and breast cancer. Elledge, Richard M. Osborne, C Kent. University of Texas Health Science Center, San Antonio, TX 78284-7884, USA.

BMJ 314 : 1843 (Published 28 June 1997).
<http://www.bmj.com/content/314/7098/1843.full>
ESR1 is co-expressed with closely adjacent uncharacterized genes spanning a breast cancer susceptibility locus at 6q25.1. Anita K. Dunbier, Helen Anderson, Zara Ghazoui,Elena Lopez-Knowles, Sunil Pancholi, Ricardo Ribas,Suzanne Drury, Kally Sidhu, Alexandra Leary, Lesley-Ann Martin, Mitch Dowsett. May 12th, 2011. London, United Kingdom.

<http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1001382>