Aug 18 : Temple University’s researchers might have discovered the mechanism that silences the estrogen receptor gene alpha (ER-a) in certain breast cancer cell lines.

An earlier study has found that in estrogen receptor-positive and estrogen receptor-negative mammary cell lines of women who have been affected with breast cancer, the tumour-suppressing gene pRb2/p130 binds to a specific region of the estrogen receptor gene alpha and forms molecular complexes recruiting and/or interacting with several proteins.

It was discovered that in estrogen receptor-negative cells, which are able to silence the expression of the estrogen receptor, pRb2/p130 forms a specific molecular complex recruiting a different sequence of proteins than in the estrogen receptor–positive cells.

As part of the current study, Antonio Giordano, Marcella Macaluso and colleagues showed that the presence of specific pRb2/p130 multimolecular complexes bound to the estrogen receptor gene strongly correlates with the methylation (chemical modification) of the gene.

“Our hypothesis is that the sequence of epigenetic events for establishing and maintaining the silenced state of the estrogen receptor gene alpha during the breast cancer progression is mediated by pRb2/p130 in association with specific proteins that modified the DNA structure through specific mechanisms,” Giordano said.

The study provided a basis for understanding how the complex pattern of estrogen receptor gene alpha methylation and transcriptional silencing is generated, as well as for understanding the relationship between this pattern and its function during breast cancer progression.

By understanding this mechanism of how pRb2/p130 recruits molecules, the researchers will be able to design therapies and drugs that are very precise in the target they recognize.

The findings of the study, ‘Epigenetic Modulation of Estrogen Receptor-a by pRb Family Proteins: A Novel Mechanism in Breast Cancer’ were published in the August issue of the journal Cancer Research. (ANI)

Tags:Breast-Cancer