Cyclin D1 (CCND1) expression is involved in estrogen receptor beta (ERβ) in human prostate cancer.
BACKGROUND
Estrogen receptor beta (ERβ) has been demonstrated to be expressed in prostate carcinoma cells and estrogen signals through ERβ to act as a tumor suppressor in prostate cancer patients. ERβ is thought to regulate the cell cycle of prostate carcinoma cells by controlling the expression of cell cycle regulators including cyclin D1 (CCND1). This interaction is of particular interest as CCND1 has been implicated in the development of prostate cancer.


METHODS
We evaluated ERβ and CCND1 immunoreactivity in human prostate cancer (n = 112, surgical specimens), and correlated the findings with clinicopathological features of the patients. Subsequent in vitro experiments using PC-3 prostate carcinoma cells were also performed to examine whether estradiol (E2) could change the expression level of CCND1 mRNA.


RESULTS
CCND1 immunoreactivity was detected in 78/112 cases (70%), and was significantly correlated with incidence of perineural invasion and ERβ immunoreactivity (P < 0.05). Forty-eight hours incubation with E2 (10 nM) increased the expression level of CCND1 mRNA as well as c-jun (JUN) and c-fos (FOS) in PC-3 cells, and PHTPP (ERβ antagonist) suppressed E2 -induced expression of those mRNAs.


CONCLUSIONS
These findings suggest that CCND1 expression is possibly regulated by estrogens via ERβ and that this signaling pathway may influence prostate cancer development.
Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan. yasu-naka@patholo2.med.tohoku.ac.jp
Yasuhiro
Y
Nakamura
Saulo J A
SJ
Felizola
Yumi
Y
Kurotaki
Fumiyoshi
F
Fujishima
Keely M
KM
McNamara
Takashi
T
Suzuki
Yoichi
Y
Arai
Hironobu
H
Sasano
D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology
C530104:CCND1 protein, human; D047629:Estrogen Receptor beta; D019938:Cyclin D1