Quantitative profiles of the mRNAs of ER-alpha and its novel variant ER-alpha36 in breast cancers and matched normal tissues.
OBJECTIVE
The novel estrogen receptor-alpha (ER-alpha) variant ER-alpha36 is reported to be functional in the estrogen signaling pathway and is related to tamoxifen resistance in breast cancer. However, ER-alpha36 tends to be a favorable factor for survival in patients without tamoxifen therapy. To investigate the mechanisms behind this paradox, we determined the differences between the transcriptional profiles of ER-alpha36 and full-length ER-alpha (ER-alpha66) in breast cancers and matched normal tissues.


METHODS
We analyzed ER-alpha36 and ER-alpha66 messenger RNA (mRNA) levels in 74 pairs of breast cancers and matched normal tissues using a real-time quantitative polymerase chain reaction (PCR) assay, and correlated the results with their clinicopathological characteristics.


RESULTS
Breast cancers expressed lower ER-alpha36 mRNA levels than matched normal tissues regardless of their ER-alpha66 expression status. Down-regulation of ER-alpha36 mRNA was correlated with local progression, lymph node metastasis, and advanced cancer stage. The level of ER-alpha66 mRNA was lower in ER-alpha negative breast cancers compared with matched normal tissues. No differences in ER-alpha66 mRNA levels were observed during cancer progression.


CONCLUSIONS
Down-regulation of ER-alpha36 is associated with carcinogenesis and progression of breast cancer.
Zheng
Yi
Y
Cancer Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
Zhang
Jing
J
Xu
Zhen-zhen
ZZ
Sheng
Jian-ming
JM
Zhang
Xiao-chen
XC
Wang
Hao-hao
HH
Teng
Xiao-dong
XD
Liu
Xiao-jiao
XJ
Cao
Jiang
J
Teng
Li-song
LS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D017931:DNA Primers / Q000235:genetics; D015536:Down-Regulation; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics* / Q000378:metabolism*
D017931:DNA Primers; D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D012334:RNA, Neoplasm