Establishment and characterization of a steroidogenic human granulosa-like tumor cell line, KGN, that expresses functional follicle-stimulating hormone receptor.
We established a steroidogenic human ovarian granulosa-like tumor cell line, designated KGN, from a patient with invasive ovarian granulosa cell carcinoma. KGN had a relatively long population doubling time of about 46.4 h and had an abnormal karyotype of 45,XX, 7q-, -22. A steroid analysis of the cultured medium by RIA performed 5 yr after the initiation of culture showed that KGN was able to secrete pregnenolone and progesterone, and both dramatically increased after stimulation with (Bu)(2)cAMP. However, little or no secretion of 17alpha-hydroxylated steroids, dehydroepiandrosterone, androstenedione, or estradiol was observed. The aromatase activity of KGN was relatively high and was further stimulated by (Bu)(2)cAMP or FSH. These findings showed a pattern similar to that of steroidogenesis in human granulosa cells, thus allowing analysis of naturally occurring steroidogenesis in human granulosa cells. Fas-mediated apoptosis of KGN was also observed, which mimicked the physiological regulation of apoptosis in normal human granulosa cells. Based on these findings, this cell line is considered to be a very useful model for understanding the regulation of steroidogenesis, cell growth, and apoptosis in human granulosa cells.
Nishi
Y
Y
Department of Medicine and Bioregulatory Science (Third Department of Internal Medicine), Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan.
Yanase
T
T
Mu
Y
Y
Oba
K
K
Ichino
I
I
Saito
M
M
Nomura
M
M
Mukasa
C
C
Okabe
T
T
Goto
K
K
Takayanagi
R
R
Kashimura
Y
Y
Haji
M
M
Nawata
H
H
D017209:Apoptosis / Q000187:drug effects; D001141:Aromatase / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology; D018929:Cell Culture Techniques / Q000379:methods; D002455:Cell Division; D002869:Chromosome Aberrations; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D006106:Granulosa Cell Tumor / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007621:Karyotyping; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D011284:Pregnenolone / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D011962:Receptors, FSH / Q000378:metabolism*; D011994:Recombinant Proteins; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D011962:Receptors, FSH; D011994:Recombinant Proteins; D011374:Progesterone; D003994:Bucladesine; D011284:Pregnenolone; D007371:Interferon-gamma; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP; D001141:Aromatase; D013755:Tetradecanoylphorbol Acetate