We have located links that may give you full text access.
The presence of a membrane-bound progesterone receptor induces growth of breast cancer with norethisterone but not with progesterone: A xenograft model.
Maturitas 2017 August
OBJECTIVES: During menopausal hormone therapy (MHT) a possible increase in breast cancer risk is thought to depend mainly on the progestogen component. In vitro studies have shown that the progesterone receptor membrane component 1 (PGRMC1) is important for tumor proliferation induced by progestogens. The primary aim of this study was to compare for the first time the natural progestogen, progesterone (P), with a synthetic progestogen, norethisterone (NET), using a xenograft model.
METHODS: MCF7 cells, transfected with PGRMC1 plasmid or empty vector, were injected into nude mice and estradiol (E2) pellets were implanted. After 12days, NET or P or placebo pellets were implanted. Tumor volumes in all groups (6 mice/group) were monitored for 6-7 weeks. Immunohistochemical expression of PGRMC1 and KI-67 was assessed. These experiments were repeated using T47D cells.
RESULTS: Compared with the control condition, E2 and sequential E2/NET combination increased xenograft tumor growth with MCF7 and T47D cells that transgenically expressed PGRMC1 (p<0.01); progesterone did not increase growth. Breast cancer cells transfected with empty vectors did not respond to either progestogen. Comparing KI-67 and PGRMC1 expression, the Pearson correlation was r=0.848, p=0.002.
CONCLUSIONS: E2 plus NET increases tumor growth in human breast cancer cells overexpressing PGRMC1, but there is no change with progesterone. To our knowledge, this is the first comparison of both progestogens in vivo using nude mice, which are frequently used in xenograft models. Clinical trials are needed to determine whether women with overexpression of PGRMC1 are at increased risk of breast cancer if NET instead of progesterone is used in MHT.
METHODS: MCF7 cells, transfected with PGRMC1 plasmid or empty vector, were injected into nude mice and estradiol (E2) pellets were implanted. After 12days, NET or P or placebo pellets were implanted. Tumor volumes in all groups (6 mice/group) were monitored for 6-7 weeks. Immunohistochemical expression of PGRMC1 and KI-67 was assessed. These experiments were repeated using T47D cells.
RESULTS: Compared with the control condition, E2 and sequential E2/NET combination increased xenograft tumor growth with MCF7 and T47D cells that transgenically expressed PGRMC1 (p<0.01); progesterone did not increase growth. Breast cancer cells transfected with empty vectors did not respond to either progestogen. Comparing KI-67 and PGRMC1 expression, the Pearson correlation was r=0.848, p=0.002.
CONCLUSIONS: E2 plus NET increases tumor growth in human breast cancer cells overexpressing PGRMC1, but there is no change with progesterone. To our knowledge, this is the first comparison of both progestogens in vivo using nude mice, which are frequently used in xenograft models. Clinical trials are needed to determine whether women with overexpression of PGRMC1 are at increased risk of breast cancer if NET instead of progesterone is used in MHT.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app