PPARgamma and Wnt/beta-Catenin pathway in human breast cancer: expression pattern, molecular interaction and clinical/prognostic correlations.
OBJECTIVE
Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor expressed in a large number of human cancers and plays important roles in breast cancer cell proliferation. Its association with clinicopathologic features and Wnt/beta-Catenin signaling pathway, a crucial factor in embryonic and malignant development, in breast cancer has not been reported systematically. In the present study, expression patterns, interaction and the correlations with clinical/prognostic factors of PPARgamma and beta-Catenin were investigated among patients with breast cancer.


METHODS
Using immunohistochemistry, we performed a study on 70 patient-derived human breast tumors and compared the protein expression levels of PPARgamma, beta-Catenin and Ki-67. Correlations were then analyzed between IHC-assessed level of these molecules and major clinicopathologic variables and survival. Furthermore, western blot (WB) analysis before and after immunoprecipitation with PPARgamma and beta-Catenin were performed on breast cancer tissues and cell lines to evaluate their protein level and molecular interaction.


RESULTS
We showed that PPARgamma expression was of significant prognostic value in the outcome of breast carcinomas, which positively correlated with ER status (P = 0.012) and inversely associated with histologic grade (P = 0.012), tumor size (P = 0.007), axillary lymph node status (P = 0.044), TNM stage (P = 0.026), Ki-67 (P = 0.006) and abnormal beta-Catenin expression (P = 0.023), whereas no correlation was seen between PPARgamma and age (P = 0.513), histology (P = 0.764), PR (P = 0.099) or HER-2 status (P = 0.175). Kaplan-Meier survival curves of the study population showed that high expression level of PPARgamma significantly correlated with long-term survival. Molecular interaction could also be demonstrated between PPARgamma and beta-Catenin both in breast cancer cell lines and tissue samples.


CONCLUSIONS
On the basis of these results, we suggested that PPARgamma might serve as a future target for the development of novel treatments in breast cancer.
Jiang
Ying
Y
Department of General Surgery, Zhongshan Hospital, Fudan University, 200032 Shanghai, China. jiangy05@yahoo.com
Zou
Lin
L
Zhang
Chunhui
C
He
Song
S
Cheng
Chun
C
Xu
Junfei
J
Lu
Weiqi
W
Zhang
Yong
Y
Zhang
Hua
H
Wang
Donglin
D
Shen
Aiguo
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D047495:PPAR gamma / Q000032:analysis / Q000502:physiology*; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology*; D015996:Survival Rate; D051153:Wnt Proteins / Q000032:analysis / Q000502:physiology*; D051176:beta Catenin / Q000032:analysis / Q000502:physiology*
D019394:Ki-67 Antigen; D047495:PPAR gamma; D011960:Receptors, Estrogen; D051153:Wnt Proteins; D051176:beta Catenin