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The protein that helps the enemy

A certain essential protein increases the expression of another protein in cancer cells in the uterus - and this transforms its skin, encourages them to divide and thus contributes to the spread of the tumor

Migration of the p21 protein from the nucleus to the cytoplasm during cancerous transformation. On the left: a normal fallopian tube with p21 in the nucleus, on the right: an ovarian cancer with p21 that has moved to the cytoplasm, and in the middle: a premalignant lesion with p21 that is partly in the nucleus and partly in the cytoplasm
Migration of the p21 protein from the nucleus to the cytoplasm during cancerous transformation. On the left: a normal fallopian tube with p21 in the nucleus, on the right: an ovarian cancer with p21 that has moved to the cytoplasm, and in the middle: a premalignant lesion with p21 that is partly in the nucleus and partly in the cytoplasm

The division of cells in our body should take place in an orderly and controlled manner. If it gets out of control, the cells continue to divide without control and a mass of cells is formed - a cancerous tumor. Some of the types of cancer that attack women are gynecological - develop in the organs that make up the reproductive system. The most common of these are uterine cancer and ovarian cancer.

Dr. Ruth Peretz, senior physician in the oncology department and head of the laboratory for female tumors at the Rambam Medical Center, researches women's cancers, mainly gynecological. She mostly focuses on ovarian cancer - the fifth most common malignant disease among women aged 65 and over in Israel. It is usually devoid of typical symptoms, so it is discovered at a late stage - when it is already very distended in the abdomen and pelvis. Its early detection increases the chances of survival to about 95%.

Studies from recent years have examined tissues taken from ovaries that were excised in preventive surgery (the purpose of which is to reduce the risk of ovarian cancer) and have diagnosed pre-cancerous cells in them. This is how they discovered that the common type of ovarian cancer (epithelial cancer, which develops in the cells that cover the organ) actually starts in the fallopian tubes and from there spreads to the ovaries. Dr. Peretz and her team were partners in proving this discovery, which led to the search for new ways of early diagnosis of ovarian cancer (now it is based more on the examination of the fallopian tubes).

Today, Dr. Peretz and her team are researching - with the help of a research grant from the National Science Foundation - the development of tumors in the fallopian tubes and uterus. One of their findings is the role of a protein called PAX8 - which is essential for the embryonic development of the fallopian tubes and uterus, apparently due to its contribution to cell growth. It remains in these organs throughout life and is essential to their identity (found mainly in them, and when they lose it they die). And if cancerous cells develop in the fallopian tubes and uterus, it also prevents their death and thus contributes to their continued spread. The research of Dr. Peretz and her team showed that if this protein is eliminated, the cancer cells die.

In their latest study, the researchers sought to examine the importance of PAX8 in uterine cancer. They studied cancer cells from human uterine tumors (samples taken during hysterectomy and cell cultures) using molecular methods, and discovered that PAX8 increases the expression of a protein called p21. Normally, p21 is found in the cell nucleus and prevents cells from dividing (inhibits DNA replication, and is therefore recognized as an anti-cancer protein. But when the cells become cancerous, it leaves the cell nucleus and moves to the cytoplasm, thus encouraging the cells to divide (in a mechanism that is not sufficiently known) Dr. Peretz explains: "We saw that in most cases of uterine cancer, the role of p21 changes completely - from an anti-cancerous protein it becomes pro-cancerous because it is in the wrong place in the cell, in the cytoplasm instead of the nucleus. This finding has therapeutic significance. If we manage to take p21 and put it back into the nucleus - we can stop the division and spread of cancer cells in the fallopian tubes (thus preventing ovarian cancer) and in the uterus. There are already drugs that prevent proteins from leaving the nucleus into the cytoplasm. We may be able to use them to treat women in whom the p21 transition process has begun, thus stopping the spread of a tumor in the fallopian tubes, ovaries and uterus. Another therapeutic option is to inhibit PAX8 in advance, but as of now, it is still difficult to implement."

Life itself:

Dr. Ruth Peretz (45) is married to a professor of astrophysics at the Technion, they have three children (17, 16, 9) and they live in Moshav Yodafat in the Galilee. At the end of 2019, they decided to take a break and went on a trip around the world ("We discovered Zoom before everyone else"). For a year they traveled in the USA, Costa Rica, Australia and New Zealand ("We arrived in the last country with the outbreak of the corona virus. It was completely closed and we were the only tourists").