Regulation of estrogen receptors alpha and beta in human breast carcinoma by exogenous leptin in nude mouse xenograft model.
BACKGROUND
It is essential to clarify the interactions of hormones during the progression of human breast cancer. This study examined the effects of exogenous human leptin on estrogen receptor (ER) alpha and beta in human breast tumor tissue in a nude mouse xenograft model.


METHODS
We created nude mice xenografts of MCF-7 human breast cancer cells, and randomly divided them into an experimental group and a control group. The mice in experimental group were injected subcutaneously around tumors with human leptin, while the control group were injected with the same dose of normal saline. A real-time RT-PCR assay was developed to quantify the mRNA of ERalpha, beta in the tumor tissues. Western blotting analyses were used to assess the relative quantities of the ERalpha, beta proteins.


RESULTS
Leptin-treated xenografted nude mice were successfully established. The amount of ERalpha mRNA was significantly higher in the leptin group than in the control group (P < 0.01), while the amount of ERbeta mRNA was significantly lower in the leptin group than in the control group (P < 0.01). Western blotting analyses revealed that the ERalpha protein level was significantly higher in the leptin group than in the control group (P < 0.01), while the ERbeta protein level was significantly lower in the leptin group than in the control group (P < 0.01).


CONCLUSIONS
Nude mouse xenograft model can be safely and serviceably treated with human leptin by subcutaneous injections around tumor. ERalpha, beta were both targets of leptin in breast cancer. Leptin can up-regulate the expression of ERalpha and down-regulate the expression of the ERbeta in human breast tumor.
Yu
Wei
W
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Gu
Jun-chao
JC
Liu
Jian-zhong
JZ
Wang
Shao-hong
SH
Wang
Yu
Y
Zhang
Zhong-tao
ZT
Ma
Xue-mei
XM
Song
Mao-min
MM
D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D020738:Leptin / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D011897:Random Allocation; D023041:Xenograft Model Antitumor Assays
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D020738:Leptin; D012333:RNA, Messenger