title: Expression of Müllerian inhibiting substance type II receptor and antiproliferative             effects of MIS on human cervical cancer.
abstract: This study aimed to analyze expression of Müllerian inhibiting substance             type II receptor (MISRII) protein and mRNA in cervical neoplasia, to demonstrate             the growth inhibition of cervical cancer cells by administration of highly purified             recombinant human Müllerian inhibiting substance (MIS) and, furthermore, to evaluate             the clinical significance of MIS as a biological modifier for MIS receptor expressing             tumors. Reverse transcriptase polymerase chain reaction (RT-PCR) was used for             MISRII mRNA expression, and in situ hybridization and immunohistochemistry were             used to observe expression, location of MISRII mRNA and protein, respectively.             To demonstrate the effect of MIS on the viability of cervical cancer cells, methyl             thiazole tetrazolium (MTT) assay was performed. Flow cytometry was used to evaluate             the cell cycle distribution after exposure to MIS in cervical cancer cells, and             the annexin-V-FITC staining method was performed to demonstrate apoptosis by MIS             in cervical cancer cells. Expression of MISRII protein and mRNA were observed             in all normal cervical and cervical carcinoma tissues. There was no significant             difference in expression of MISRII protein and MISRII mRNA between normal cervical             and cervical carcinoma tissues. MTT assay showed negative correlation between             MIS exposure time and the viability of cervical cells (P=0.008). The changes in             cell cycle distribution after MIS exposure suggest that MIS plays an important             role in inducing cellular apoptosis by causing arrest at the G1 phase and increasing             cells at sub-G0G1 phase. Annexin-V-FITC staining methods showed that cellular             apoptosis was, respectively, 10.44 and 12.89% after 24 and 48 h of MIS exposure             in cervical carcinoma cells. There was a negative correlation between cellular             survival and MIS exposure time. This study demonstrates that MISRII is present             on normal cervical and cervical carcinoma tissues, and MIS shows receptor-mediated             antiproliferative effect on cervical cells in vitro. These data suggest that MIS             may be used as a biological modifier or therapeutic modulator on MISRII-expressing             tumors in the future.
authors.affiliation: Department of Obstetrics and Gynecology, The Catholic University                     of Korea, Seoul, Republic of Korea.
authors.forename: Jae Yen
authors.initials: JY
authors.lastname: Song
authors.forename: Hyun Hee
authors.initials: HH
authors.lastname: Jo
authors.forename: Mee Ran
authors.initials: MR
authors.lastname: Kim
authors.forename: Young Oak
authors.initials: YO
authors.lastname: Lew
authors.forename: Ki Sung
authors.initials: KS
authors.lastname: Ryu
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Cha
authors.forename: Chang Suk
authors.initials: CS
authors.lastname: Kang
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Donahoe
authors.forename: David T
authors.initials: DT
authors.lastname: MacLaughlin
authors.forename: Jang Heub
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D054304:Anti-Mullerian Hormone / Q000494:pharmacology*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D015870:Gene Expression; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D018931:Antineoplastic Agents, Hormonal; D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; C084621:anti-Mullerian hormone receptor; D054304:Anti-Mullerian Hormone