Linchpin Gene Discovered -- MEDICA - World Forum for Medicine

The study, led by Ronald Weigel, M.D., Ph.D., professor and head of surgery at the University of Iowa Roy J. and Lucille A. Carver College of Medicine, reveals a central role for transcription factor AP2C (TFAP2C) in controlling multiple pathways of oestrogen signalling.

"Oestrogen binds to oestrogen receptors and triggers a cascade of events including gene regulation," said Weigel. "We found that elimination of the TFAP2C from the cell causes all of those cascades that we associate with oestrogen to go away. The treated cancer cells were not able to respond to oestrogen by any normal pathway."

The researchers found that silencing expression of TFAP2C in hormone-responsive breast cancer cells significantly decreased the amount of ER-alpha made by the cancer cell. This reduction in ER-alpha (down to 16 percent of the level normally made by breast cancer cells) also affected production of other "downstream" genes involved in cancer growth.

In addition, silencing the TFAP2C also knocked out expression of another oestrogen receptor called GPR30 that is found at the cancer cell membrane. Importantly, the team also showed that these effects inhibited tumour growth. Specifically, the treated cancer cells did not grow in response to oestrogen and establishment of tumours in mice was delayed.

The finding suggests that there are many pathways that allow cells to respond to oestrogen, and that TFAP2C is a central player in controlling hormone response. "Targeting this gene may be a better way to develop drugs to treat hormone-responsive breast cancers because it targets multiple different pathways," Weigel said.; Source: University of Iowa