The role of IRX3 gene in oestrogen dependent (ER+) and oestrogen independent (ER-) human breast cancer
1 Formål
ER+ breast cancer is one of the most common form of cancer and 30% of patients develop resistance to current treatments. There is therefore a great need to discover and target novel mechanisms in the growth and progression of this cancer type. We have discovered that IRx3 gene is selectively up regulated in ER+ breast cancer, and knockdown of this gene in the ER+ breast cancer cell lines reduces cell growth in vitro. We therefore want to investigate whether this effect translates in vivo, by injecting wild type, knockdown and knockout ER+ breast cancer cells in the mammary fat pad of immunodeficient mice and monitor tumor growth and metastatic spread. An ER+ cell line (MCF-7) will be compared with an ER- cell line (MDA-MB-231).
2 Skadevirkninger
Mice will develop breast cancer and metastases, but they will be euthanised before the general condition will be impaired. For this reason we classify the severity of the experiment as moderate.
3 Forventet nytteverdi
Disrupting this gene or resulting protein function could serve as an adjuvant or alternative treatment, especially for patients developing resistance to standard of care therapy, which could improve patient survival and recovery.
4 Antall dyr og art
89 female immuno-defficient mice
5 Hvordan etterleve 3R
The main objective of the experiment is to identify if IRX3 deficiency has an impact on tumor growth and metastases in vivo. Tumor development and metastatic spread cannot be tracked in vitro.
The smallest possible groups to provide a statistically significant power will be used.
The implantation of cancer cells will be achieved under anaesthesia. The animals will receive analgesia post implantation and will be monitored closely by project members. Experienced technicians will monitor the animals and they will early discover any sign of illness and take the decision of euthanasia, if necessary. All cages will have environmental enrichment available at the animal facility.
ER+ breast cancer is one of the most common form of cancer and 30% of patients develop resistance to current treatments. There is therefore a great need to discover and target novel mechanisms in the growth and progression of this cancer type. We have discovered that IRx3 gene is selectively up regulated in ER+ breast cancer, and knockdown of this gene in the ER+ breast cancer cell lines reduces cell growth in vitro. We therefore want to investigate whether this effect translates in vivo, by injecting wild type, knockdown and knockout ER+ breast cancer cells in the mammary fat pad of immunodeficient mice and monitor tumor growth and metastatic spread. An ER+ cell line (MCF-7) will be compared with an ER- cell line (MDA-MB-231).
2 Skadevirkninger
Mice will develop breast cancer and metastases, but they will be euthanised before the general condition will be impaired. For this reason we classify the severity of the experiment as moderate.
3 Forventet nytteverdi
Disrupting this gene or resulting protein function could serve as an adjuvant or alternative treatment, especially for patients developing resistance to standard of care therapy, which could improve patient survival and recovery.
4 Antall dyr og art
89 female immuno-defficient mice
5 Hvordan etterleve 3R
The main objective of the experiment is to identify if IRX3 deficiency has an impact on tumor growth and metastases in vivo. Tumor development and metastatic spread cannot be tracked in vitro.
The smallest possible groups to provide a statistically significant power will be used.
The implantation of cancer cells will be achieved under anaesthesia. The animals will receive analgesia post implantation and will be monitored closely by project members. Experienced technicians will monitor the animals and they will early discover any sign of illness and take the decision of euthanasia, if necessary. All cages will have environmental enrichment available at the animal facility.