How estrogen feeds breast tumors

A new study is providing insight into how estrogen fuels many breast cancers, and researchers say the findings could lead to new cancer-fighting drugs.

Researchers found that estrogen inhibits a protein called MLK3 that causes normal cell death. Blocking MLK3 leads to uncontrolled growth of cancer cells and resistance to chemotherapy.

Researchers from Loyola University Health System and three other centers reported the findings in the journal Cancer Research.

“This could give us a new angle to treating breast cancer,” said senior author Ajay Rana, PhD, a professor in the Department of Pharmacology at Loyola University Chicago Stritch School of Medicine.

About 60 percent of all breast cancers are estrogen-positive or progesterone-positive. This means the cancer cells have receptors for the female hormones estrogen and progesterone. Consequently, the hormones fuel the tumor's growth.

In laboratory experiments, researchers found that in estrogen-positive and progesterone-positive cancer cells, there is a reduction in the activity of MLK3. Consequently, cells can continue growing, changing and developing resistance to chemotherapy. “Cancer cells are very smart,” Dr. Rana said.

By contrast, Dr. Rana's team found that MLK3 activity was much higher in estrogen-negative and progesterone-negative cancer cells.

The next step, Dr. Rana said, is to look for a drug that would overcome the inhibitory effect of estrogen on MLK3. Such a drug would be taken in combination with chemotherapy drugs.

Loyola co-authors are Velusamy Rangasamy, PhD (first author); Rajakishore Mishra, PhD; Suneet Mehrotra, PhD; Gautam Sondarva, PhD, Rajarshi S.Ray, PhD and Basabi Rana, PhD. Other co-authors are Arundhati Rao, MD, of Scott and White Hospital in Temple, Tx and Malay Chatterjee, PhD of Jadavpur University in Kolkata, India. Basabi Rana and Ajay Rana also are affiliated with Edward Hines Jr. VA Hospital.

Based in the western suburbs of Chicago, Loyola University Health System is a quaternary care system with a 61-acre main medical center campus, the 36-acre Gottlieb Memorial Hospital campus and 25 primary and specialty care facilities in Cook, Will and DuPage counties. The medical center campus is conveniently located in Maywood, 13 miles west of the Chicago Loop and 8 miles east of Oak Brook, Ill. The heart of the medical center campus, Loyola University Hospital, is a 561-licensed-bed facility. It houses a Level 1 Trauma Center, a Burn Center and the Ronald McDonald® Children's Hospital of Loyola University Medical Center. Also on campus are the Cardinal Bernardin Cancer Center, Loyola Outpatient Center, Center for Heart & Vascular Medicine and Loyola Oral Health Center as well as the LUC Stritch School of Medicine, the LUC Marcella Niehoff School of Nursing and the Loyola Center for Fitness. Loyola's Gottlieb Memorial Hospital campus in Melrose Park includes the 264-bed community hospital, the Gottlieb Center for Fitness and the Marjorie G. Weinberg Cancer Care Center.