Scientists Identify Molecular Link Between Estrogen Receptors and Invasive Growth in Breast Cancer
Emory University and Winship Cancer Institute scientists have discovered a link between estrogen receptors -- the molecules that bind the estrogen hormone to cells -- and invasive growth of breast cancer. The finding could help explain the mechanisms leading to breast cancer progression and could have important consequences for drugs that are aimed at blocking estrogen receptors. The research is published in the journal Cell.
Estrogen receptors regulate normal breast cell growth and development. The presence or absence of estrogen receptors in breast cancer patients is a critical prognostic indicator of breast cancer progression. Approximately 70% of breast tumors contain estrogen receptors and are dependent on estrogen for their growth. These breast cancers -- called "estrogen receptor positive" tumors -- are routinely treated or prevented by a class of drugs known as selective estrogen receptor modulators (SERMS), including drugs such as tamoxifen, which block the estrogen receptors. Breast tumors lacking estrogen receptors -- called "estrogen receptor negative" tumors -- are not affected by estrogen antagonist drugs, and thus generally have a much less favorable prognosis.
In seeking the genetic alterations that cause breast cancers to lose their dependence on estrogen receptors for growth (becoming estrogen receptor negative), the Emory scientists discovered that a protein called MTA3 is part of an estrogen-dependent pathway that regulates the expression of other "downstream" molecules, including the cell adhesion molecule called E-cadherin. Cell adhesion molecules are responsible for maintaining normal cellular structure, and the loss or underexpression of these molecules has been associated with invasive growth of breast cancer.