Expression of DCC and netrin-1 in normal human endometrium and its implication in endometrial carcinogenesis.
OBJECTIVE
Although DCC has been considered as a candidate tumor suppressor, the roles it plays in the uterine endometrium and in the carcinogenic process remains unclear. To define these roles more clearly, we examined the expression of DCC and its ligand, netrin-1, in the normal endometrium and in endometrial cancer.


METHODS
The expression of DCC and netrin-1 in normal endometrial glands and in cancer cell lines was examined by RT-PCR and immunohistochemistry. The effects of exogenous DCC and netrin-1 expression were observed together with the respective expression vector transfection.


RESULTS
Endometrial glands in the proliferative and early secretory phase expressed both DCC and netrin-1, but glands in the late-secretory phase tended to silence DCC expression. In addition, all of the endometrial cancer cell lines lost normal DCC expression. Restored DCC expression in the cancer cell lines in the absence of netrin-1 induced apoptosis. However, no changes were observed in the presence of netrin-1.


CONCLUSIONS
Our observations suggest that DCC/netrin-1 signaling may commit cells to the transition of endometrial gland architecture or function from a proliferating to a secretory phase. In addition, the silencing of DCC expression may contribute to the escape of endometrial cancer cells from a DCC-regulated apoptotic program, thereby promoting malignant phenotypes.
Kato
H D
HD
Department of Molecular Genetics, Division of Molecular and Cell Therapeutics, Medical Institute of Bioregulation, Kyushu University, Beppu City, Oita 874-0838, Japan. hidekato@tsurumi.beppu.kyushu-u.ac.jp <hidekato@tsurumi.beppu.kyushu-u.ac.jp>
Kondoh
H
H
Inoue
T
T
Asanoma
K
K
Matsuda
T
T
Arima
T
T
Kato
K
K
Yoshikawa
T
T
Wake
N
N
D000328:Adult; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D000075389:DCC Receptor; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism* / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D000075388:Netrin-1; D011956:Receptors, Cell Surface; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501909:DCC protein, human; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1