Expression of midkine and pleiotropin in ovarian tumors.
OBJECTIVE
To compare the expression of midkine and pleiotropin in malignant ovarian tumors with that in normal and benign ovarian tissue.


METHODS
Total RNA was isolated from 23 samples of normal ovaries, 15 benign ovarian tumors, and 36 malignant ovarian tumors. Midkine and pleiotropin gene expression was examined by using Northern blot analysis. To confirm the localization of midkine expression, in situ hybridization and immunohistochemical analyses were performed. The truncated midkine messenger RNA was examined using polymerase chain reaction with complementary DNA synthesized from total RNA with reverse transcriptase.


RESULTS
Expression of midkine gene was observed in 19 of 23 normal ovary samples and in 51 of 53 ovarian tumors (13 of 15 benign, both of the two borderline tumors, and all 36 malignant tumors). Pleiotropin gene was expressed in six normal ovaries and in 24 tumors (nine benign, two borderline, and 13 malignant tumors). The expression of midkine in germ cell tumors was significantly lower than in epithelial tumors, whereas expression in malignant epithelial tumors was significantly higher than in benign ones. In germ cell tumors, two samples with differentiated neural tissues showed high levels of pleiotropin gene expression. In situ hybridization and immunohistochemical analysis showed strong expression of midkine in cancer cells. The truncated midkine messenger RNA was not found in any of the normal, benign, or malignant tissues examined.


CONCLUSIONS
These results suggest an association between midkine and carcinogenesis. Expression of pleiotropin is more restricted, and high levels of its expression may be correlated with neural differentiation.
Nakanishi
T
T
Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Japan.
Kadomatsu
K
K
Okamoto
T
T
Tomoda
Y
Y
Muramatsu
T
T
D000328:Adult; D000368:Aged; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006133:Growth Substances / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D008875:Middle Aged; D000078792:Midkine; D010049:Ovarian Diseases / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics
D002352:Carrier Proteins; D016207:Cytokines; D006133:Growth Substances; D012333:RNA, Messenger; C066845:pleiotrophin; D000078792:Midkine