Researchers at Baylor College of Medicine have brought to light some new information regarding the development of uterine cancer, the most common gynecological cancer in the United States. With Dr. Martin M. Matzuk at the helm, the team found that Transforming Growth Factor beta (TGF-beta) signaling pathways in uterine cells can actually prevent the disease.
The first of the two published studies details how TGF can suppress the overgrowth and transformation of healthy cells into cancerous ones at the level of the endometrium, the membrane lining the inside of the uterus.
Laboratory experiments tested the theory on mouse models lacking a certain TGF protein, receptor ALK5. The molecule mediates pathway signaling to the cells, and in its absence, the tumors began growing and spreading.
“The mice lacking ALK5 developed metastatic endometrial tumors with cervical and vaginal masses. The tumors were estrogen-dependent, meaning they required estrogen to grow. When the ovaries – the natural source of estrogen – were removed, both the tumors and metastases to the lungs regressed”, noted Dr. Diana Monsivais, instructor of Pathology and Immunology.
The second study explored circumstances where two other proteins were missing – Smad2 and Smad3, which transmit the signal from the TGF-beta receptors to the nucleus.
“I found that disrupting these particular proteins, Smad2 and Smad3 in mice, caused a very aggressive hyperplasia or overgrowth of the endometrium that rapidly developed into cancer and death”, explained Maya Kriseman, doctor of Obstetrics and Gynecology. “These effects were dependent on estrogen, which also is a characteristic of the most common type of uterine cancer in humans. These and other findings give us a better idea as to why these mice develop aggressive uterine tumors and escape normal endometrial regulation”.
Results of these tests help paint a more complete picture regarding the processes and mechanisms that influence and lead to the development of the disease.
“Taken together, the findings of Monsivais and Kriseman strongly suggest that the TGF-beta pathway is a tumor-suppressor mechanism in the uterus”, concluded Dr. Matzuk.
Dr. William E. Gibbons, director of reproductive endocrinology and infertility at Baylor College of Medicine, added: “By revealing that the TGF-beta pathway plays a protective role against uterine cancer, this work has significantly advanced our understanding of the disease and opened novel avenues for future therapeutic strategies”.
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