Identification of large-scale characteristic genes of Müllerian inhibiting substance in human ovarian cancer cells.
The purpose of this study was to investigate the large-scale characteristic molecular signature of Müllerian inhibiting substance (MIS) in human ovarian cancer cells through expression genomics. To understand the comprehensive molecular mechanisms by which MIS inhibits ovarian cancer cell growth, we identified the large-scale characteristic molecular changes elicited by MIS in the human ovarian cancer cell line OVCAR-8, using DNA microarray analysis. Combined serial gene expression analysis from 0 to 96 h after MIS treatment of OVCAR-8 cells resulted in 759 genes which showed at least a 2-fold change in overexpression or underexpression compared to non-treatment groups. Of the 759 outlier genes, 498 genes were mapped to known biological cellular processes, and the resultant major pathways included metabolism, signal transduction, cell growth and apoptosis. Among these pathways, 68 genetic elements were dissected as cell cycle-related genes induced by MIS. Although cellular phenotypic changes by MIS were observed after 24 h of treatment, the characteristic large-scale molecular changes were observed from 48 to 96 h of exposure to MIS. This finding may imply that the suppressive role of MIS on ovarian cancer cells could be cumulative in that the metabolic disturbance of MIS is followed by arrest at the G1/S cell cycle checkpoint. We suggest 759 outlier genes comprise the characteristic molecular signature of MIS, which may be responsible for the suppressive effect on OVCAR-8 cells. Although the precise biological mechanisms underlying these outlier genes should be validated, the genetic elements described herein provide promising therapeutic interventions for ovarian cancer.
Department of Pathology, Microdissection Genomics Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Suk Woo
SW
Nam
Yun Sung
YS
Jo
Jung Woo
JW
Eun
Jae Yen
JY
Song
Ki Sung
KS
Ryu
Jung Young
JY
Lee
Joon Mo
JM
Lee
David T
DT
Maclaughlin
Jang Heub
JH
Kim
D054304:Anti-Mullerian Hormone / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D054304:Anti-Mullerian Hormone