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- Silins, Ilvars, et al.
(författare)
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Letter to the editor - Reply
- 2003
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Ingår i: Gynecologic Oncology. - 1095-6859 .- 0090-8258. ; 89:2, s. 339-339
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 4. |
- Horvath, György, 1942, et al.
(författare)
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Function of the exon 7 deletion variant estrogen receptor alpha protein in an estradiol-resistant, tamoxifen-sensitive human endometrial adenocarcinoma grown in nude mice.
- 2002
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Ingår i: Gynecologic oncology. - : Elsevier BV. - 0090-8258. ; 84:2, s. 271-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In addition to hormone and DNA binding, interactions, including competition with other proteins, appear to be a critical component of transcriptional regulation by the estrogen receptor alpha (ER(alpha)). In vitro studies suggest that exon deletion (Delta exon) variant forms of ER(alpha) may also play an important role in determining the progression from hormone dependence to hormone independence in receptor positive tumors. METHODS: We investigated the presence of ERalpha mRNA and protein variants and their possible role in a moderately differentiated human endometrial adenocarcinoma grown in nude mice. In addition to wild-type (wt), RT-PCR assay of the tumor revealed the presence of two mRNA variants, a low concentration of Delta5 and a high concentration of Delta7 ER(alpha). We detected wt, Delta7, and Delta5,7 mRNA by sequencing the transcripts after stable transfection of three HeLa cells with either splice variant. The linked in vitro translation/transcription assay of the transfected cells and the Western blot analysis of the original tumor generated both wt (66 kDa) and Delta7 (52 kDa), Delta5,7 (46 kDa) ER(alpha) proteins. RESULTS: Tumor growth was characterized as estradiol and progesterone resistant but tamoxifen sensitive, i.e., neither estradiol nor progesterone treatment altered the growth rate, whereas tamoxifen treatment significantly increased the tumor volume doubling time. Estradiol treatment decreased the wt and increased the Delta7 variant ER(alpha) protein expression significantly in a dose-dependent manner. Tamoxifen treatment, however, increased the expression of both proteins whereas progesterone had no effect. Estradiol treatment did not influence expression of the Delta5,7 variant protein, which increased significantly in the tamoxifen-treated tumors. Gel mobility shift assays revealed that both wt and Delta7 ER(alpha) proteins bind to the consensus DNA sequence, whereas the Delta5,7 variant protein did not. CONCLUSIONS: We conclude that estradiol, tamoxifen, and progesterone regulate wt and variant ER(alpha) mRNA and protein expression separately and differently and that this hormonal regulation probably occurs, via different mechanisms, at the transcriptional or posttranscriptional level. The Delta7 variant ER(alpha) may play a crucial role in the determination of hormone sensitivity and thus in the outcome of hormone treatment of human endometrial adenocarcinomas.
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- Ivarsson, Karin, 1970, et al.
(författare)
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Production of steroids by human ovarian surface epithelial cells in culture: possible role of progesterone as growth inhibitor.
- 2001
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Ingår i: Gynecologic oncology. - : Elsevier BV. - 0090-8258. ; 82:1, s. 116-21
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Tidskriftsartikel (refereegranskat)abstract
- The purpose was to investigate whether normal ovarian surface epithelial cells, harvested from premenopausal and postmenopausal women, are capable of steroid production, and to evaluate effects of estradiol and progesterone on growth regulation of such cells.Ovarian surface epithelial cells were obtained by brushing of the ovarian surface of 9 premenopausal and 10 postmenopausal women undergoing surgery for benign gynecological diseases. The conditioned media after culture, with and without addition of FSH and LH, were analyzed for estradiol and progesterone. The proliferative effects of the steroids were analyzed using two different culture models, nonconfluent cells and confluent cells, and two different detection methods, [(3)H]thymidine incorporation and a colorimetric method assaying cell number.The normal ovarian surface epithelial cells were found to secrete both estradiol and progesterone, a production that was not regulated by FSH or LH. Addition of steroids to the cultured cells did not induce any overall significant growth effects. However, progesterone significantly inhibited the growth of ovarian surface epithelial cells from three of the patients. Enhanced thymidine incorporation was observed in the presence of the progesterone receptor antagonist Org 31710 in the nonconfluent cultures of cells from postmenopausal women, but no effect of an estrogen receptor antagonist was observed.The normal ovarian surface epithelium is capable of steroid production, which is also often observed in tissue from ovarian epithelial tumors. Progesterone appeared to be a negative regulator of ovarian surface epithelial growth, while estradiol had no effect.
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| 6. |
- Jin, Yuesheng, et al.
(författare)
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Cytogenetic and molecular genetic characterization of immortalized human ovarian surface epithelial cell lines: consistent loss of chromosome 13 and amplification of chromosome 20
- 2004
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 92:1, s. 183-191
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. This study aimed at identifying the genetic events involved in immortalization of ovarian epithelial cells, which might be important steps in ovarian carcinogenesis. Methods. The genetic profiles of five human ovarian surface epithelial (HOSE) cell lines immortalized by retroviral transfection of the human papillomavirus (HPV) E6/E7 genes were thoroughly characterized by chromosome banding and fluorescence in situ hybridization (FISH), at various passages pre- and post-crisis. Results. In pre-crisis, most cells had simple, non-clonal karyotypic changes. Telomere association was the commonest aberration, suggesting that tolermase dysfunction might be an important genetic event leading to cellular crisis. After immortalization post-crisis, however, the karyotypic patterns were non-random. Loss of genetic materials was a characteristic feature. The commonest numerical aberrations were -13, -14, -16, -17, -18, and +5. Among them, loss of chromosome 13 was common change observed in all lines. The only recurrent structural aberration was homogeneously staining regions (hsr) observed in three lines. FISH and combined binary ratio labeling (COBRA)-FISH showed in two cases that the lists were derived from chromosome 20. Clonal evolution was observed in four of the lines. In one line, hsr was the only change shared by all subclones, suggesting that it might be a primary event in cell immortalization. Conclusion. The results of the present study suggested that loss of chromosome 13 and the amplification of chromosome 20 might be early genetic events involved in ovarian cell immortalization, and might be useful targets for the study of genomic aberrations in ovarian carcinogenesis. (C) 2003 Elsevier Inc. All rights reserved.
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| 7. |
- Koul, Anjila, et al.
(författare)
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Two BRCA1-positive epithelial ovarian tumors with metastases to the central nervous system: a case report
- 2001
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 80:3, s. 399-402
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cerebral metastasis secondary to ovarian cancer is a rare phenomenon. While no clear relationship to known prognostic factors is found, others suggest this as a biologically diverse behavior of ovarian cancer. CASES: In a pilot study, 37 invasive epithelial ovarian cancer samples were analyzed to detect the frequency of BRCA1/BRCA2 mutations in the south of Sweden (results published). A retrospective follow-up revealed that 2 of these (2/37; 5.4%) patients developed central nervous system metastases during the course of their disease. Both patients had advanced surgical stage disease at the time of diagnosis, with histopathological serous type tumors that were negative for estrogen and progesterone receptors. One of these patients carried a germline BRCA1 mutation, whereas a somatic BRCA1 mutation was identified in the other patient. CONCLUSIONS: To the best of our knowledge the molecular genetic profile of these tumors is not found in the literature and it is suggested that such analyses could provide some insight for a better understanding of this rare phenomenon.
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