Abstract:
BACKGROUND:Telomerase is a ribonucleoprotein enzyme that synthesises telomeres in human germ cells, embryogenesis and in cancer, maintaining chromosomal length, stability and cellular immortality. The hTERT gene is the rate-limiting determinant of telomerase reactivation during immortalization and malignant transformation. Telomeric DNA-binding proteins have been attracting increasing interest due to their essential role in the regulation of telomeric DNA length and in protecting against chromosomal end-to-end fusion. These proteins include hTR, TRF1, TRF2, TANK1, TANK2, POT1, TIN2, EST1, and TEP. This study represents the first comprehensive investigation of the mRNA expression of key telomere-related genes in human breast cancer. METHODS:One hundred and twenty seven tumour tissues and 33 normal tissues were analyzed. Levels of transcription of hTERT, hTR, TRF1, TRF2, TANK1, TANK2, POT1, TIN2, EST1, and TEP1 were determined using real-time quantitative PCR. The mRNA expression of these genes was normalized against CK19 and was then analyzed against the pathological parameters and clinical outcome over a 10 year follow up period. RESULTS:The mRNA expressions of hTERT, hTR, TANK1, EST1, and TEP1 were higher in tumour samples compared with normal breast tissue. This reached statistical significance for EST1 when comparing good prognosis tumours with normal breast tissue (means=11013 vs 1160, P=0.05). Both hTERT and TEP1 levels significantly predicted overall survival (P=0.012 and 0.005 respectively) and disease-free survival (P=0.0011 and 0.01 respectively). The mRNA levels of TANK2 and POT1 were lower in malignant tissues compared with non-malignant breast tissues and this difference reached statistical significance when comparing the levels in normal tissues with those in advanced tumours (P=0.0008 and P=0.038 respectively). Their levels fell further with increasing tumour's stage and were higher in tumours from patients who remained disease free compared with those who developed local recurrence or distant metastasis or died from breast cancer.TRF2 showed a trend similar to that of TANK2 and POT1. Furthermore, there was a highly significant correlation between TANK1 expression and that of hTERT, hTR, TRF1, TRF2 and EST1, (r=0.533, 0.586, 0.608, 0.644 and 0.551 respectively, P<0.001). CONCLUSIONS:Genes encoding telomere-associated proteins display different patterns of mRNA expression in human breast cancer, and in normal breast tissue, suggesting different and sometimes opposing roles in mammary carcinogenesis. hTERT, hTR, TANK1, EST1 and TEP1 seem to be up-regulated, with hTERT and TEP1 correlating with clinical outcome. Conversely, TANK2 and POT1 transcription levels demonstrate a compelling trend to be lower in malignant tissues and lower still in those patients who develop recurrent disease suggesting that TANK2 and POT1 may act as tumour suppressor genes possibly by negatively regulating telomerase activity.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Salhab M,Jiang WG,Newbold RF,Mokbel Kdoi
10.1007/s10549-007-9622-8subject
Has Abstractpub_date
2008-05-01 00:00:00pages
35-46issue
1eissn
0167-6806issn
1573-7217journal_volume
109pub_type
杂志文章abstract::Mammographic density is a strong risk factor for breast cancer; however the mechanism that underlies this association is unclear. We hypothesized that measures of energy balance early in life and in adulthood may be associated with mammographic density. We conducted a cross-sectional analysis of 1,398 women in the Nur...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-007-9631-7
更新日期:2008-05-01 00:00:00
abstract::The rate of contralateral prophylactic mastectomy (CPM) is rising rapidly, despite limited evidence about the procedure's relative benefits and harms. The objective of this study is to examine the impact of CPM on life expectancy (LE) and quality-adjusted life expectancy (QALE) in women with sporadic unilateral breast...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-015-3462-8
更新日期:2015-07-01 00:00:00
abstract:PURPOSE:Preoperative paravertebral blocks (PPVBs) are routinely used for treating post-mastectomy pain, yet uncertainties remain about the cost-effectiveness of this modality. We aim to evaluate the cost-effectiveness of PPVBs at common willingness-to-pay (WTP) thresholds. METHODS:A decision analytic model compared tw...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/s10549-017-4371-9
更新日期:2017-10-01 00:00:00
abstract::Identification of novel targets for the treatment of basal-like breast cancer is essential for improved outcomes in patients with this disease. This study investigates the association of MMP7 expression and MMP7 promoter methylation with subtype and outcome in breast cancer patient cohorts. Immunohistochemical analysi...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-014-2989-4
更新日期:2014-07-01 00:00:00
abstract::Monitoring effective antiestrogenic activity of the triphenylethylenes in patients with breast cancer is usually determined by the duration of response. The pharmacokinetics of toremifene and tamoxifen have been shown to be highly variable but patient specific. In the present study, we developed a method to accurately...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01832356
更新日期:1992-01-01 00:00:00
abstract:OBJECTIVE:This study examined the influence of knowledge of clinical information on the accuracy of mammography in women referred for investigation of breast symptoms. METHODS:Subjects were sampled from all women consecutively attending a symptomatic breast clinic and aged 25-55 years. This included all 240 women show...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/B:BREA.0000025416.66632.84
更新日期:2004-06-01 00:00:00
abstract::The tumor-stroma ratio has previously been shown to be prognostic for patients with invasive breast cancer. We present a validation study to assess the prognostic significance in lymph node-negative, premenopausal patients from the perioperative chemotherapy trial (POP trial, 10854) conducted by the European Organizat...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2571-5
更新日期:2013-06-01 00:00:00
abstract::Although preoperative magnetic resonance imaging (MRI) can detect mammographically occult contralateral breast cancers (CBCs) among women with ductal carcinoma in situ (DCIS), the impact of MRI on the incidence of subsequent CBC events is unclear. We examined whether MRI use decreases CBC occurrences and detection of ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-016-3858-0
更新日期:2016-07-01 00:00:00
abstract::Xeroradiography of the axilla was performed in 132 patients with operable breast cancer to investigate the status of the axillary lymph nodes. Pathologic findings were correlated with the results of clinical examination and xeroradiographic findings. Xeroradiography does not appear to have improved our ability to iden...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01807590
更新日期:1983-01-01 00:00:00
abstract::To determine whether capecitabine schedule adaptation improves the tolerability of capecitabine-paclitaxel combination therapy for metastatic breast cancer (MBC), patients with anthracycline-pretreated HER2-negative MBC were randomized to either arm A (21-day cycles: capecitabine 1,000 mg/m(2) twice daily, days 1-14; ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10549-011-1776-8
更新日期:2012-01-01 00:00:00
abstract::Histological grading of 160 primary infiltrating breast carcinomas showed that both oestrogen and progesterone receptor status are strongly related to grade, tumours that are receptor positive tending to be of lower grade than the receptor negative. The nuclear factors used in grading were those that determined this a...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01806938
更新日期:1982-01-01 00:00:00
abstract::In the context of neoadjuvant therapy (NT) for breast cancer patients, different targeted therapy approaches are currently evaluated in clinical trials. Serum markers could help to monitor and optimize such treatment strategies. We investigated human epidermal growth factor receptor 2 serum (sHER2) levels in 175 breas...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s10549-010-1030-9
更新日期:2010-09-01 00:00:00
abstract::Intraoperative radiotherapy with electrons (ELIOT) after conservative surgery for breast carcinoma was introduced at the IEO in 1999 as a research programme. The results on 1,822 patients treated from January 2000 to December 2008 are reported. Women with unicentric primary breast carcinoma of less than 2.5 cm in the ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-010-1115-5
更新日期:2010-11-01 00:00:00
abstract::Long-term estrogen deprivation treatment for breast cancer can, in some patients, lead to the activation of alternate cellular pathways, resulting in the re-emergence of the disease. This is a distressing scenario for oncologists and patients, but recent intensive molecular and biochemical studies are beginning to unr...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/s10549-007-9697-2
更新日期:2007-01-01 00:00:00
abstract:PURPOSE:Breast density (BD), an important risk factor for breast cancer, can change over time in some women, but the underlying mechanism is unclear. Very little is known about the impact of surgical weight loss on BD. Our hypothesis is that weight loss after bariatric surgery is associated with a significant and favor...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-017-4361-y
更新日期:2017-10-01 00:00:00
abstract:RATIONALE:Survival after loco-regional failure (LRF) of breast cancer was investigated at the population level. METHODS:Using the Stockholm cancer registry, 2698 patients diagnosed with LRF between 1980 and 2014 were identified and divided into three cohorts by year of LRF diagnosis. Post-relapse event-free survival (...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-018-4936-2
更新日期:2018-12-01 00:00:00
abstract::Cytoplasmic HuR is associated with reduced survival in invasive breast cancer. We designed this study to determine the predictive and prognostic value of HuR expression in women with breast cancer who underwent neoadjuvant chemotherapy followed by surgical resection. We immunohistochemically analyzed cytoplasmic HuR e...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2679-7
更新日期:2013-09-01 00:00:00
abstract::Mammography and ultrasound are often used concurrently for patients with palpable breast masses. While mammography has a false-negative rate of approximately 15 %, the addition of breast ultrasound decreases this rate among patients with palpable breast masses. There are no recent outcome data regarding the use of com...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-015-3557-2
更新日期:2015-10-01 00:00:00
abstract::To determine the incidence of microsatellite instability (MSI) and its relationship with both clinicopathologic parameters and patient survival, 101 cases of breast cancer were investigated. In addition, transforming growth factor-beta (TGF-beta) receptor type II (RII) gene mutation was also examined to clarify the re...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1006167210269
更新日期:1999-01-01 00:00:00
abstract:PURPOSE:Cytokine milieu of tumor microenvironment affects tumorigenesis in breast cancer. The aim of the present study was to investigate the potential association of functional single nucleotide polymorphisms (SNPs) in TNF-LTA locus with breast cancer. METHODS:The study included 127 individuals comprising 40 breast c...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-008-0006-5
更新日期:2009-03-01 00:00:00
abstract:BACKGROUND:The aim was to prove the low identification rate of sentinel lymph node biopsy (SNB) and to determine the feasibility of replacing axillary lymph node dissection (AND) in axillary lymph node positive patients after chemotherapy. METHODS:From October 2001 to July 2005, 875 consecutive patients with primary o...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章
doi:10.1007/s10549-006-9330-9
更新日期:2007-05-01 00:00:00
abstract::The prognostic value of epidermal growth factor receptor (EGF-R) was prospectively assessed in a series of 229 clinical T1-T2, N0-N1 breast carcinomas diagnosed between May 1987 and October 1989. EGF-R expression was determined by measuring the specific Bmax of 125I EGF to tumor plasma membrane preparations. Tumor wit...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF00666480
更新日期:1994-01-01 00:00:00
abstract:PURPOSE:Chronic upper extremity disability (UED) is common after breast cancer treatment but under-identified and under-treated. Although UED has been linked to quality of life (QoL), the role of UED as mediator between contemporary treatment practices and QoL has not been quantified. This investigation describes UED i...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-019-05184-1
更新日期:2019-06-01 00:00:00
abstract::Serum melatonin (MLT) levels have been reported to diminish significantly by the 5th and 6th decades of life as the incidence of breast cancer increases. Given MLT's anti-cancer activity, we hypothesize that age-related decline in pineal MLT production leads to enhanced breast cancer development and growth as women ag...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-010-0958-0
更新日期:2011-05-01 00:00:00
abstract:PURPOSE:TP53 mutation is the most common mutation in breast cancer, and it is considered a target marker of triple-negative breast cancer (TNBC). We investigated whether expression of p53 detected by immunochemical staining predicts the chemotherapy response of TNBC. METHODS:A total of 11,393 TNBC patients who had bet...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-018-4928-2
更新日期:2018-11-01 00:00:00
abstract::As the number of women surviving breast cancer increases, with implications for the health system, research into the physical and psychosocial sequelae of the cancer and its treatment is a priority. This research estimated self-reported health-related quality of life (HRQoL) associated with two rehabilitation interven...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-005-5151-5
更新日期:2005-10-01 00:00:00
abstract:PURPOSE:We studied which, age of the patient or density of the breast accounts for the sensitivity of mammography and ultrasonography (US). Furthermore we studied whether the overall impression on the density of the breast or the density in tumour area accounts for the sensitivity of mammography and ultrasonography. M...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1010627527026
更新日期:2001-05-01 00:00:00
abstract:BACKGROUND:In several neoplastic diseases, immunosuppression has been shown to correlate with disease stage, progression, and outcome. As the prognosis for metastatic breast cancer is still pessimistic, additional strategies are being sought to improve survival. Local immunosuppression in sentinel node biopsies from 24...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1016009913699
更新日期:2002-07-01 00:00:00
abstract:PURPOSE:The effect of tea consumption on breast cancer survival remained to be explored. Meanwhile, green tea favorably facilitates lipid metabolisms in breast cancer survivors. This study aimed to examine the effect of tea consumption and the interactions with lipids on breast cancer survival. METHODS:A total of 1551...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-019-05253-5
更新日期:2019-08-01 00:00:00
abstract::The high potency and selectivity of new aromatase inhibitors has translated to greater efficacy and improved tolerability in comparison with established second-line hormonal agents for advanced breast cancer in phase III clinical trials. Two pharmacological studies are reported which assess the use of one of these inh...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章
doi:10.1023/a:1006289811540
更新日期:1999-07-01 00:00:00