Individual transcriptional activity of estrogen receptors in primary breast cancer and its clinical significance.
To predict the efficacy of hormonal therapy at the individual-level, immunohistochemical methods are used to analyze expression of classical molecular biomarkers such as estrogen receptor (ER), progesterone receptor (PgR), and HER2. However, the current diagnostic standard is not perfect for the individualization of diverse cases. Therefore, establishment of more accurate diagnostics is required. Previously, we established a novel method that enables analysis of ER transcriptional activation potential in clinical specimens using an adenovirus estrogen response element-green fluorescence protein (ERE-GFP) assay system. Using this assay, we assessed the ERE transcriptional activity of 62 primary breast cancer samples. In 40% of samples, we observed that ER protein expression was not consistent with ERE activity. Comparison of ERE activity with clinicopathological information revealed that ERE activity was significantly correlated with the ER target gene, PgR, rather than ER in terms of both protein and mRNA expression. Moreover, subgrouping of Luminal A-type breast cancer samples according to ERE activity revealed that ERα mRNA expression correlated with ER target gene mRNA expression in the high-, but not the low-, ERE-activity group. On the other hand, the low-ERE-activity group showed significantly higher mRNA expression of the malignancy biomarker Ki67 in association with disease recurrence in 5% of patients. Thus, these data suggest that ER expression does not always correlate with ER transcriptional activity. Therefore, in addition to ER protein expression, determination of ERE activity as an ER functional marker will be helpful for analysis of a variety of diverse breast cancer cases and the subsequent course of treatment.
Department of Molecular and Functional Dynamics, Graduate School of Medicine, Tohoku University Aoba-Ku, Sendai, 980-8575, Japan.
Tatsuyuki
T
Gohno
Yuko
Y
Seino
Toru
T
Hanamura
Toshifumi
T
Niwa
Mitsuyo
M
Matsumoto
Nobuo
N
Yaegashi
Hanako
H
Oba
Masafumi
M
Kurosumi
Hiroyuki
H
Takei
Yuri
Y
Yamaguchi
Shin-Ichi
S
Hayashi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000235:genetics*; D004967:Estrogens / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D049452:Green Fluorescent Proteins; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D011980:Receptors, Progesterone / Q000096:biosynthesis* / Q000235:genetics; D015533:Transcriptional Activation
C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004967:Estrogens; D019394:Ki-67 Antigen; D011980:Receptors, Progesterone; D049452:Green Fluorescent Proteins
Breast cancer; ERE transcriptional activity; Ki67; Luminal A; estrogen receptor α