United States Jefferson University, Philadelphia, Thomas Jefferson University, Kimmel Cancer Center and New York, Albert Einstein College of Medicine researchers found that in the early stage of breast cancer gene mutations play an important role, Under normal circumstances, the gene can prevent breast cancer development.
Jefferson Medical College professor of Cancer Biology, Michael P. Lisanti, Jefferson Kimmel Cancer Center director Richard Pestell, Ph.D. led the study team found that nearly 19% of breast cancer patients carry mutations Caveonlin-1 gene, while the breast cancer cells by estrogen are usually – so called ‘estrogen receptor-positive’ cells. The group also discovered six new Caveolin-1 mutations associated with breast cancer. Nearly 35% of such breast cancers may carry Caveonlin-1 mutant gene. Dr. Lisanti says, Caveonlin proteins in cell communication, plays an important role, but also with a number of diseases such as cancer, arteriosclerosis, diabetes, Alzheimer’s disease and muscular dystrophy.
In the American Journal of Pathology, the researchers reported in this study. They claimed that the results could prompt Caveonlin-1 mutant gene in estrogen-positive breast cancer plays an important role, while 70% of breast cancer are of this type.
This is the first demonstration that a specific Caveonlin-1 mutation is exclusively connected to being estrogen-receptor positive. Dr. Lisanti says he also raised in all the cancer samples, all of the estrogen receptor-negative patients did not Caveonlin mutant gene.
“1 / 3 of the estrogen receptor-positive patients carrying mutations Caveonlin, so it is the most common illness among people mutation. ‘He said,’ is usually about 70% of breast cancers are estrogen receptor-positive and 30% are negative, that is 1 / 3 of patients with type. ”
Dr. Lisanti explains that he and his colleagues wanted to test the hypothesis that the “functional Caveonlin-1 gene lead to loss of the increase in cancer incidence, or increase the expression of estrogen receptor.” Usually only 5-10% of breast cells express estrogen receptors, but in cancer and certain causes fatal damage to the receptor activity has markedly increased.
Dr. Lisanti’s team developed a lack of Caveolin-1 gene in mice and found that breast tissues in mice, estrogen receptor number and activity were significantly increased, especially in the mammary epithelial cells, it will stimulate cell growth. Caveolin-1, Dr. Lisanti claimed that as a switch gene, as control of receptor activity and cell proliferation.
“This is the first time we found that the absence of Caveolin Gene Expression in the upregulation of estrogen receptor play an important role. This helps to explain the organization from non-lethal to lethal transformation of the organization.”
Dr. Lisanti explains that estrogen receptors are thought to help turn on certain genes such as cyclin D1 gene, which in turn promote cancer development. “We have thought of a research method of breast cancer genes, and in this, we would say that estrogen receptor-generated cyclin D1 gene, which can cause breast cancer. But now we have added another kinds of relationships: caveolin gene inactivation is the first step. ”
The team found that cyclin D1 in human breast cancer gene activity increased, especially after receiving estrogen therapy patients. “Essentially, we have designed a preclinical model to study the development of breast cancer estrogen and the role of Caveolin gene deletion, which for the understanding of caveolin gene inactivation in breast cancer as a first step in a new way. We do a good . ”
The group subsequently showed in laboratory studies, lack of caveolin gene in mouse mammary cells in the absence of growth-stimulating factor under the action of estrogen receptor also increased. Therefore, they concluded, estrogen receptor, two factors increase the need: Caveolin gene inactivation and growth factor depletion.
These findings may have clinical significance. According to Dr. Lisanti said, those who estrogen receptor-positive and caveolin gene mutations in breast cancer patients do not carry the same mutation in caveolin gene compared with patients more likely to relapse.
