Monday, March 1, 2010

How Does Estrogen Feed Breast Cancer Tumors?

Loyola Study Finds the Hormone Inhibits a Protein that Causes Normal Cell Death

MAYWOOD, Ill. -- 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.

About Loyola University Health System

Loyola University Health System (LUHS) is part of Trinity Health. Based in the western suburbs of Chicago, LUHS is a quaternary care system with a 61-acre main medical center campus, the 36-acre Gottlieb Memorial Hospital campus and more than 30 primary and specialty care facilities in Cook, Will and DuPage counties. Loyola University Medical Center’s campus is conveniently located in Maywood, 13 miles west of Chicago’s Loop and 8 miles east of Oak Brook, Ill. At the heart of the medical center campus is a 559-licensed-bed hospital that 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 Loyola University Chicago Stritch School of Medicine, Loyola University Chicago Marcella Niehoff School of Nursing and the Loyola Center for Fitness. Loyola's Gottlieb campus in Melrose Park includes the 255-licensed-bed community hospital, the Professional Office Building housing 150 private practice clinics, the Adult Day Care, the Gottlieb Center for Fitness, Loyola Center for Metabolic Surgery and Bariatric Care and the Loyola Cancer Care & Research at the Marjorie G. Weinberg Cancer Center at Melrose Park.

Trinity Health is a national Catholic health system with an enduring legacy and a steadfast mission to be a transforming and healing presence within the communities we serve. Trinity is committed to being a people-centered health care system that enables better health, better care and lower costs. Trinity Health has 88 hospitals and hundreds of continuing care facilities, home care agencies and outpatient centers in 21 states and 119,000 employees.