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ABSTRACT: Although more than five variant forms of estrogen receptor-beta (ERbeta) have been identified, their role has not been identified. This study was carried out to investigate the changes of ERbeta variants in breast cancer development.
Using reverse transcription polymerase chain reaction (RT-PCR) and triple primer PCR (TP-PCR), the expression levels of ERbeta variants mRNA were measured in 66 paired normal and cancer tissues. The relative expression level of ERbeta variants were compared between normal and cancer tissues, and also compared according to various clinicopathological parameters.
Among ERbeta variants, ERbeta2 and ERbeta5 consist of the major proportion of ERbeta expression both in normal and cancer tissues. The ERbeta and ERbeta2 expression levels decreased significantly in the cancers compared with corresponding normal tissues, particularly in ERalpha-expressing cancers. However, ERbeta5 expression level increased significantly in the cancers, especially in those of postmenopausal patients. The relative increase of ERbeta5 expression in cancer tissues was associated with favorable differentiation.
Decrease of ERbeta2 is thought to be the key reason for the decrease in ERbeta expression in cancer tissues, and it is particularly associated with the development of ERalpha-expressing breast cancer.
Journal of Surgical Oncology 06/2006; 93(6):504-10. · 2.10 Impact Factor
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ABSTRACT: The effects of exercise on bone density have been found to be inconsistent in previous studies. We conducted a cross-sectional study in premenarcheal girls to test two hypotheses to explain these inconsistencies. Firstly, "the intensity of mechanical strain, in terms of the ground reaction force(GRF), has more important effects on the bone mass at a weight-bearing site", and secondly, "calcium intake modifies the bone response to exercise".
The areal bone mineral density was measured at the Os calcis, using peripheral dual energy X-ray absorptiometry, in 91 premenarcheal girls aged between 9 and 12 years. The intensity of mechanical strain of exercise was assessed by a self-report questionnaire and scored by the GRF as multiples of body weight, irrespective of the frequency and duration of exercise. The energy and calcium intake were calculated from the 24-hour dietary recall. An analysis of covariance(ANCOVA) was used to determine the interaction and main effects of exercise and calcium on the bone density, after adjusting for age, weight, height and energy intake.
The difference in the bone density between moderate and low impact exercise was more pronounced in the high than low calcium intake group. The bone density for moderate impact exercise and high calcium intake was significantly higher than that for low impact exercise (p=0.046) and low calcium intake, after adjusting for age, weight, height and energy intake.
Our study suggests that the bone density at a weight-bearing site is positively related to the intensity of mechanical loading exercise, and the calcium intake may modify the bone response to exercise at the loaded site in premenarcheal girls.
Journal of Preventive Medicine and Public Health 09/2005; 38(3):291-7.
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ABSTRACT: Using messenger RNA (mRNA) in situ hybridization, we investigated estrogen receptor-beta (ERbeta) mRNA levels in normal mammary, benign breast tumor (BBT), breast cancer (BC), and metastatic lymph node tissues to verify the role of ERbeta in BC development and progression. ERbeta expression was significantly decreased in BC and metastatic lymph node tissues compared with normal mammary and BBT tissues (p < 0.01). The intensity and extent of ERbeta mRNA signals were also significantly lower in BC and metastatic lymph node tissues than in the normal mammary and BBT tissues (p < 0.01). An inverse relationship was found between ERbeta mRNA level and both histologic grade (p = 0.091) and progesterone receptor expression (p = 0.052) with marginal significance, but no significant association was noted between ERbeta expression in cancer tissues and the other clinico-pathologic data. The 3-year distant relapse-free survival probability was found to be independent of ERbeta expression. Collectively, ERbeta mRNA decreases in the process of BC development, but seems to be associated with poor differentiation.
Breast Cancer Research and Treatment 07/2003; 80(1):79-85. · 4.43 Impact Factor
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ABSTRACT: A humanized monoclonal antibody against HER2 has been using in a clinical setting and has been shown to possess therapeutic properties. A mimetic peptide against HER2 was also reported to bind to the HER2 receptor with some therapeutic potential. Based on a previous report and the sequence of Herceptin, we designed oligonucleotides of anti-HER2 mimetic peptides, named V2 and V3 peptides, in order to develop a peptide- producing vector system for biologic therapy against HER2- overexpressing cancers. We also adopted the sequence of a previously reported mimetic peptide, V1 (Park BW et al. Nat. Biotechnol, 2000, 18:194-198), as a reference peptide. We examined the effects of the V2 and V3 peptides against the HER2-overexpressing cell lines, SK-BR-3 and T6-17. Transient transfection of the construct expressing V1 and V2 inhibited cell proliferation in HER2-overexpressing cell lines by 20 - 30%, but had no effect on the HER2-negative NIH3T3 cells. The proliferation inhibition shown by V2 was slightly better than that shown by V1. Recombinant peptides V2 and V3 were produced on a large scale in an E. coli system, and the V2 peptide showed anti-HER2-specific tumor cell proliferation inhibition of 10% to 30%. Current results suggest that anti-HER2 mimetic peptides, overexpressed by a constitutive promoter or produced in an E. coli system, could specifically inhibit the proliferation of HER2-expressing cancer cells. Further efforts to augment the biologic specificity and efficacy and to develop new technologies for the purification of the peptide from the E coli system are needed.
Yonsei Medical Journal 03/2003; 44(1):58-64. · 1.14 Impact Factor
