Navigation Links
Why chemotherapy causes more infertility in women than in men
Date:2/22/2011

Chemotherapeutic agents, used in cancer treatment, destroy not only cancer cells but also healthy cells, thus affecting germ cells as well. Consequently, after surviving cancer many female patients are confronted with the diagnosis: infertility. For a long time a relationship between infertility and chemotherapeutic agents has been assumed, but until now, the exact mechanism was not known.

Scientists from the research group of Prof. Volker Dtsch (Institute of Biophysical Chemistry, Goethe University Frankfurt) in cooperation with international partners have now started to unveil the mechanism of cancer treatment related infertility. Their results are published in the internationally renowned journal Cell. Mainly women suffer from infertility because the quality control in the oocytes is different from male germ cells. Male germ cells are produced throughout the whole life span but the number of female germ cells is restricted and already fixed before birth. If the oocytes are damaged during cancer treatment, they are destroyed by the female quality control mechanism.

Essential for this process is the protein p63 which shows striking similarity to another important protein of the same family: p53. p53 is also named "guardian of the genome" because of its regulatory function in cell division and cell death of damaged cells and, therefore, plays a key role in the suppression of genetic anomalies which could lead to cancer. In more than half of all human tumors p53 is altered and no longer functional.

For a long time the exact regulation of p53 and p63 and the similarities and differences between these two proteins have been the object of many international research projects. In the currently accepted model the concentration of p53 in healthy cells is relatively low. If genetic anomalies occur in a cell which could cause the transition to a cancer cell, the concentration of p53 increases and four p53 proteins form a tetramer. In this tetrameric state the tumor suppressor is active and initiates either repair of the damaged DNA or programmed cell death. Surprisingly, despite the fact that p53 and p63 show high similarity, the mechanism by which the activity of p63 is controlled in oocytes seemed to be different.

The research group of Prof. Volker Dtsch could show now that the two mechanisms that regulate the activity of p53 and of p63 are closely related, but distinct. The level of p63 in normal oocytes is high and the protein is kept in a closed dimeric and inactive state. If DNA double-strand breaks occur, for example caused by radioactive radiation, p63 becomes phosphorylated. As a result of this phosphorylation, the structure of the p63 dimer changes to an open state allowing the attachment of a second phosphorylated dimer. The resulting active p63 tetramer is similar to the active p53 tetramer and leads to the death of the damaged oocyte. Many of the chemotherapeutic agents cause DNA double-strand breaks which activate p63, finally leading to the cell death of the oocytes.

The related proteins of model organisms such as Caenorhabditis elegans (nematode) are also investigated by the Dtsch group. Because of the short life span of this worm its p63 related protein does not act as a tumor suppressor but controls the genetic stability of the germ cells. The quality control of germ cells, thus, seems to be the original function of the p53 protein family and leads to the conclusion that p63 is the ancestor of the entire p53 family.

Interestingly, p63 shows an additional function: it is essential for the maintenance of stem cells in epithelial layers like skin. Because of the close similarity of stem and germ cells, this second function shows the evolutionary process of the p53 protein family from p63-like proteins, that in simple organisms are responsible for the genetic stability of germ cells, via controlling the maintenance of stem cells in organisms with renewal tissues, finally to p53-like tumor repressors in somatic cells. This demonstrates the outstanding importance of the p53 protein family for the development and health of human beings.


'/>"/>

Contact: Prof. Volker Doetsch
vdoetsch@em.uni-frankfurt.de
49-697-982-9631
Goethe University Frankfurt
Source:Eurekalert

Related biology news :

1. A loose grip provides better chemotherapy
2. Invention could improve cancer drug delivery, lessen harmful effects of chemotherapy
3. Virginia Tech engineers introduce thermotherapy as a chemotherapy alternative
4. Major component in turmeric enhance effect of chemotherapy drug in head and neck cancer
5. Novocure reports data showing TTF therapy in combination with chemotherapy has the potential to increase overall survival for patients with advanced non-small cell lung cancer
6. Identifying subsets of patients who will respond to subsequent lines of chemotherapy
7. New technology may prolong the life of implanted devices, from pacemakers to chemotherapy ports
8. TGen finds protein inhibitor revives chemotherapy for ovarian patients
9. Duke develops nano-scale drug delivery for chemotherapy
10. Common chemotherapy drug triggers fatal allergic reactions
11. CSHL team develops mouse models of leukemia that predict response to chemotherapy
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/11/2017)... MELBOURNE, Florida , April 11, 2017 ... "Company"), a security technology company, announces the appointment of independent ... John Bendheim to its Board of Directors, furthering the ... ... behalf of NXT-ID, we look forward to their guidance and ...
(Date:4/5/2017)... SEATTLE , April 5, 2017  The Allen ... the Allen Cell Explorer: a one-of-a-kind portal and dynamic ... large-scale 3D imaging data, the first application of deep ... edited human stem cell lines and a growing suite ... the platform for these and future publicly available resources ...
(Date:4/5/2017)... April 4, 2017 KEY FINDINGS ... expand at a CAGR of 25.76% during the forecast ... the primary factor for the growth of the stem ... https://www.reportbuyer.com/product/4807905/ MARKET INSIGHTS The global stem cell ... application, and geography. The stem cell market of the ...
Breaking Biology News(10 mins):
(Date:7/17/2017)... , ... July 17, 2017 ... ... technology-enabled clinical trial solutions, today announced safety software company AB Cube has ... eHealth Solutions business segment to advance technology innovation across life sciences and ...
(Date:7/17/2017)... ... July 17, 2017 , ... ... Hsing, Ph.D. , recently participated in the BiG (Biomedical Innovation Group) annual meeting ... by discussions of CAR-T (chimeric antigen receptor T-cell) therapy, a rapidly developing highly ...
(Date:7/16/2017)... N.J. (PRWEB) , ... July 16, 2017 , ... ... laboratory equipment and analytical instruments announced the launch of its new line of ... introduced five rocking and waving shaker models (both analog and digital) for laboratory ...
(Date:7/14/2017)... ... July 14, 2017 , ... ... company . Sonic Manufacturing Technologies has installed a solar system on its roof ... three-year period,” the President of Sonic, Kenneth Raab stated. The company’s proud history ...
Breaking Biology Technology: