Medroxyprogesterone acetate stimulates cdk inhibitors, p21 and p27, in endometrial carcinoma cells transfected with progesterone receptor-B cDNA.
OBJECTIVE
Progestin is reported to suppress the growth of endometrial carcinomas, although its precise mechanism of action is not clear. This study aimed to transfect progesterone receptor-B (PRB) cDNA into endometrial carcinoma cells and investigate the effect of medroxyprogesterone acetate (MPA) on cell growth, and p21 and p27 expression in the transfectant.


METHODS
Immunoblotting for p21 and p27 was performed at predetermined times after the administration of MPA.


RESULTS
PR expression was maximally induced in Ishikawa cells at 24 hrs after the transfection. At 1 x 10(-6) M, MPA suppressed the growth of the transfectant by 34% on day 6 and stimulated p21 accumulation at 48 to 72 hrs and p27 accumulation at 48 to 96 hrs after its administration. PRB cDNA was effectively transfected and in the transfectant MPA at 1 x 10(-6) M, the dosage suppressing growth, induced p21 and p27expression.


CONCLUSIONS
p21 and p27 may be related to progesterone-induced growth suppression in human endometrial adenocarcinoma.
Department of Clinical Cytology, Kitasato University Graduate School of Medical Sciences, Kanagawa, Japan.
M
M
Kawaguchi
J
J
Watanabe
M
M
Hamano
Y
Y
Kamata
T
T
Arai
Y
Y
Nishimura
A
A
Obokata
T
T
Jobo
H
H
Kuramoto
D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000187:drug effects* / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000187:drug effects* / Q000378:metabolism; D018076:DNA, Complementary / Q000032:analysis; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects*
D050759:Cyclin-Dependent Kinase Inhibitor p21; D018076:DNA, Complementary; D011980:Receptors, Progesterone; C097314:progesterone receptor B; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017258:Medroxyprogesterone Acetate