Linchpin gene may be useful target for new breast cancer therapiesSeptember 17, 2007University of Iowa researchers have discovered a gene that plays a linchpin role in the ability of breast cancer cells to respond to estrogen. The finding may lead to improved therapies for hormone-responsive breast cancers and may explain differences in the effectiveness of current treatments. Estrogen causes hormone-responsive breast cancer cells to grow and divide by interacting with estrogen receptors made by cancer cells. Interfering with estrogen signaling is the basis of two common breast cancer therapies -- tamoxifen, which blocks estrogen's interaction with a primary estrogen receptor called ER-alpha, and aromatase inhibitors that reduce the amount of estrogen the body makes and therefore affect any pathway that uses estrogen. 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 estrogen signaling. The findings are published in the Sept. 15 issue of Cancer Research. "Estrogen binds to estrogen receptors and triggers a cascade of events including gene regulation," said Weigel, who also is a member of the Holden Comprehensive Cancer Center at the UI. "We found that elimination of the TFAP2C from the cell causes all of those cascades that we associate with estrogen to go away. The treated cancer cells were not able to respond to estrogen 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 estrogen receptor called GPR30 that is found at the cancer cell membrane. Importantly, the team also showed that these effects inhibited tumor growth. Specifically, the treated cancer cells did not grow in response to estrogen and establishment of tumors in mice was delayed. The finding suggests that there are many pathways that allow cells to respond to estrogen, 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. The results also may explain why tamoxifen, which targets a single pathway, is less effective that aromatase inhibitors, which likely affect many estrogen pathways. Weigel noted that advancing understanding of estrogen regulation and hormone-response in breast cancer is just one part of a larger focus on breast health at the UI. "The UI has a great interest in breast cancer. Within the next couple of months, the UI Breast Health Clinic will be open and part of its mission is advancing both basic and clinical research in breast cancer," he said. "This study is one example of how we are moving forward in unlocking the mysteries behind what controls the ability of a breast cancer to respond to estrogen." University of Iowa |
|||||||||||||||||||||
| Related Breast Cancer Current Events and Breast Cancer News Articles Carnegie Mellon researchers link health-care debate to risk of dying in US and Europe The current health care debate in the United States is complicated. Trade-offs between heath care expenditures, lifestyle choices and life expectancy have been suggested but seldom clearly demonstrated. Scientists uncover new key to the puzzle of hormone therapy and breast cancer The use of postmenopausal hormone therapy has decreased over time in the United States, which researchers suggest may play a key role in the declining rate of atypical ductal hyperplasia, a known risk factor for breast cancer. Breast density associated with increased risk of cancer recurrence A new study finds that women treated for breast cancer are at higher risk of cancer recurrence if they have dense breasts. Published in the December 15, 2009 issue of Cancer, a peer-reviewed journal of the American Cancer Society, the study's results indicate that breast cancer patients with dense breasts may benefit from additional therapies following surgery, such as radiation. Researcher: 'Optical biopsy' for breast cancer increasingly accurate But women may not have to endure the medical costs, stress and potential complications that accompany such invasive biopsies forever. A University of Florida biomedical engineering researcher is making progress on an "optical biopsy" that has the potential to determine whether growths are cancerous without ever puncturing the skin. Plastic surgeons offer microsurgery technique for breast reconstruction, tummy tuck after mastectomy Since her teens, Jennifer Jablon had watched family members deal with breast cancer during their 40s, 50s, and 60s. She wondered whether it would be her fate too. Experimental agent reduces breast cancer metastasis to bone Researchers have reduced breast cancer metastasis to bone using an experimental agent to inhibit ROCK, a protein that was found to be over-expressed in metastatic breast cancer. American Dietetic Association Releases Updated Position Paper Promoting and Supporting Breastfeeding The American Dietetic Association has released an updated position paper on breastfeeding that details health benefits for both infants and mothers and encourages promotion of breastfeeding whenever possible. Weight Training Boosts Breast Cancer Survivors' Body Image and Satisfaction with Intimate Relationships, Penn Study Shows In addition to building muscle, weightlifting is also a prescription for self-esteem among breast cancer survivors, according to new University of Pennsylvania School of Medicine research. Early-stage, HER2-positive breast cancer patients at increased risk of recurrence Early-stage breast cancer patients with HER2 positive tumors one centimeter or smaller are at significant risk of recurrence of their disease, compared to those with early-stage disease who do not express the aggressive protein, according to a study led by researchers at The University of Texas M. D. Anderson Cancer Center. Adapting Space-Industry Technology to Treat Breast Cancer Researchers at Rush University Medical Center and Argonne National Laboratory are collaborating on a study to determine if an imaging technique used by NASA to inspect the space shuttle can be used to predict tissue damage often experienced by breast cancer patients undergoing radiation therapy. More Breast Cancer Current Events and Breast Cancer News Articles |
|||||||||||||||||||||
|
|||||||||||||||||||||
|
|||||||||||||||||||||