Abstract:
OBJECTIVES:MKK4 is a metastasis suppressor that is downregulated in some ovarian cancers. We sought to investigate whether promoter methylation, loss of heterozygosity, or changes in phosphorylation are involved in MKK4 dysregulation during ovarian carcinogenesis. METHODS:Bisulfite sequencing was used to determine MKK4 promoter methylation. PCR analysis of tumor/normal DNA was performed to determine LOH at the MKK4 locus. Normal human ovarian surface epithelium (HOSE) and SKOV-3 cells were serum starved and treated with EGF, TGFbeta, or wortmannin. Western blotting was performed using antibodies that detect total and phosphorylated MKK4. RESULTS:No MKK4 promoter hypermethylation was detected in 21 ovarian cancers. LOH was detected at the MKK4 intragenic marker D17S969 in 35% of cases and at D17S1303 in 20%. MKK4 protein was detected in 97% of ovarian tumors. The inactivated phosphoserine 80 (ser-80) form comprised 62% of phosphorylated MKK4 protein in ovarian tumors. Treatment of HOSE or SKOV-3 cells with EGF induced a 1.7- to 4.2-fold increase in phosphorylation of ser-80 MKK4 without altering total MKK4 protein. TGFbeta increased MKK4 ser-80 phosphorylation by 5.4-fold above baseline. The PI3K/Akt pathway inhibitor wortmannin decreased the amount of ser-80 MKK4 by 50%, and inhibited EGF stimulation of MKK4 ser-80 phosphorylation by 60%. CONCLUSIONS:LOH of MKK4 occurs in some ovarian cancers, but without loss of MKK4 protein. MKK4 expression does not appear to be downregulated by promoter methylation. Peptide growth factors induce MKK4 ser-80 phosphorylation, which downregulates its activity. PI3K/Akt pathway inhibitors can partially block ser-80 phosphorylation and this may have therapeutic implications.
journal_name
Gynecol Oncoljournal_title
Gynecologic oncologyauthors
Spillman MA,Lacy J,Murphy SK,Whitaker RS,Grace L,Teaberry V,Marks JR,Berchuck Adoi
10.1016/j.ygyno.2006.12.017subject
Has Abstractpub_date
2007-05-01 00:00:00pages
312-20issue
2eissn
0090-8258issn
1095-6859pii
S0090-8258(06)00973-5journal_volume
105pub_type
杂志文章abstract::Practice changing standardization of lower extremity lymphedema quantitative measurements with integrated patient reported outcomes will likely refine and redefine the optimal risk-reduction strategies to diminish the devastating limb-related dysfunction and morbidity associated with treatment of gynecologic cancers. ...
journal_title:Gynecologic oncology
pub_type: 杂志文章,评审
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更新日期:2021-02-01 00:00:00
abstract::During the period 1977 to 1985, 12 patients with FIGO stage II and III epithelial ovarian carcinoma failed to achieve a pathologic complete response with chemotherapy and underwent salvage whole-abdominal irradiation (WAXRT). Six of these patients had gross residual disease present at the time of irradiation, and thre...
journal_title:Gynecologic oncology
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abstract:OBJECTIVES:The aim of this study was to show the learning experience of the employment of laparoscopic lymphadenectomy followed by a Schauta operation to treat patients with cervical carcinoma at a university hospital and to evaluate the feasibility, complications, hospital stay, delay in return to work, and overall su...
journal_title:Gynecologic oncology
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doi:10.1006/gyno.1999.5588
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abstract::The objective of this phase II multicenter study was to assess the efficacy and tolerance of triptorelin (a sustained-release LHRH agonist) in advanced or recurrent endometrial cancer. A total of 101 monthly intramuscular injections were administered to 24 eligible patients (median number/patient = 3; range 1-12). Mai...
journal_title:Gynecologic oncology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1006/gyno.1999.5538
更新日期:1999-11-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to compare the usefulness of a new universal grading system for ovarian cancer proposed by Shimizu et al. (Cancer 82 (1998), 893; Gynecol. Oncol. 70 (1998), 2) with that of the FIGO grading system as a prognostic factor of ovarian cancer. METHODS:We reviewed all paraffin-embedded ti...
journal_title:Gynecologic oncology
pub_type: 杂志文章
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journal_title:Gynecologic oncology
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doi:10.1016/0090-8258(86)90087-9
更新日期:1986-11-01 00:00:00
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journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2005.06.065
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abstract::An unusual case of Stage IB moderately well-differentiated endometrial adenocarcinoma that was confined to a polyp and recurred only in the abdominal wound is presented. Eighteen months following complete excision, local electron beam therapy, and the institution of hormonal therapy, the patient is alive and without o...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(86)90089-2
更新日期:1986-11-01 00:00:00
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journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2007.01.011
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journal_title:Gynecologic oncology
pub_type: 杂志文章
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journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2013.12.007
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pub_type: 杂志文章
doi:10.1016/s0090-8258(03)00541-9
更新日期:2003-11-01 00:00:00
abstract:OBJECTIVE:This two-arm longitudinal study was performed within a regional organized cervical-cancer-prevention program in which HPV-DNA test is used in primary screening. The aim was to analyze the diagnostic performances of p16INK4a/Ki-67 dual-test and E6/E7-mRNA test in identifying CIN2+ lesion among HPV-DNA positive...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2012.11.030
更新日期:2013-03-01 00:00:00
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journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1994.1166
更新日期:1994-07-01 00:00:00
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journal_title:Gynecologic oncology
pub_type: 杂志文章
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journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2017.12.028
更新日期:2018-03-01 00:00:00
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journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2008.04.021
更新日期:2008-08-01 00:00:00
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journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/s0090-8258(03)00053-2
更新日期:2003-04-01 00:00:00
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journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(86)90306-9
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pub_type: 杂志文章,评审
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更新日期:2019-03-01 00:00:00
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journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(90)90304-4
更新日期:1990-04-01 00:00:00
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journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2008.07.014
更新日期:2008-11-01 00:00:00
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journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.2000.5785
更新日期:2000-05-01 00:00:00
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journal_title:Gynecologic oncology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.ygyno.2013.10.024
更新日期:2014-01-01 00:00:00
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journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2015.09.077
更新日期:2016-01-01 00:00:00
abstract::Between October 1985 and January 1989, 33 patients with stage I (31) or clinically occult stage II (2) endometrial cancer at a high risk for recurrence were entered in a prospective study evaluating adjuvant cisplatin, doxorubicin, and cyclophosphamide (PAC) chemotherapy. Eligibility criteria included grade 2 tumors w...
journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/0090-8258(90)90063-q
更新日期:1990-09-01 00:00:00
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journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/s0090-8258(03)00070-2
更新日期:2003-05-01 00:00:00
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journal_title:Gynecologic oncology
pub_type: 杂志文章
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更新日期:2016-01-01 00:00:00
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journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1016/j.ygyno.2008.09.011
更新日期:2009-01-01 00:00:00
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journal_title:Gynecologic oncology
pub_type: 杂志文章
doi:10.1006/gyno.1993.1059
更新日期:1993-03-01 00:00:00