In examinations of human breast cancer cells and human breast tumor specimens, the scientists discovered that the insulin receptor is present in two slightly different forms - small amounts of the familiar adult form which binds only insulin, and larger amounts of the fetal form which can bind either insulin or a related growth factor known as IGF-II. It is when the fetal form docks with insulin or IGF-II that rapid cell division ensues, stimulating cancer growth, the researchers found.
"In the breast tumors, the fetal form binds to both insulin and to IGF-II to stimulate tumor growth," said Goldfine. "Because of this process, the fetal form of the insulin receptor now appears to be a clear target for drugs to block or slow breast tumor growth."
The Molecular and Cellular Biology paper established that a shortened form of the insulin receptor, known as IR-A, is the fetal form, or growth-stimulating form, and that it is activated by the growth-inducing protein IGF-II. The Oncogene paper reported the group's discovery that the fetal form of the insulin receptor is "over-produced" in breast cancers, and that it is activated in breast tumors by IGF-II.
The research is a collaboration between UCSF's Goldfine and two laboratories in Italy. Senior author on the paper in Molecular and Cellular Biology is Riccardo Vigneri, MD, professor of medicine at the University of Catania. Senior author on the paper in Oncogene is Antonio Belfiore, MD, at the same institution. The laboratory of Paolo Sbraccia, MD, at the University of Rome also played a key role.
Co-authors on both papers, along with Goldfine, Vigneri and Belfiore, are
Franceso Frasca, MD, Giueseppe Pandini, MD, Pierluigi Scalia, MD, Laura Sciacca,
MD, Rosanna Mineo, MD, Angela Constantino, MD, all of University of Catania.
Contact: Wallace Ravven
University of California - San Francisco