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    Elevated Expression of CD151 Gene in Estrogen Receptor and Progesterone Receptor Positive Breast Carcinoma
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    Abstract:
    Address for correspondence and reprint requests: Ivyna Bong Pau Ni, Hematology Unit, Cancer Research Centre, Institute for Medical Research, Jalan Pahang, 50588 Kuala Lumpur, Malaysia. Tel: +603 2616 2724. Fax: +603 26162707. Email: ivyna@imr.gov.my Med & Health 2011; 6(1): 33-40 Ivyna Bong P.N. et al 34 transcriptase polymerase chain reaction (qRT-PCR) to measure the CD151 gene expression in 45 breast cancers. Our preliminary results revealed that CD151 expression is significantly higher in ER positive and PR positive breast cancers at 95% and 99% confidence intervals, respectively. In contrast, there is no significant correlation between CD151 expression and tumour grades or c-erbB-2 status at 95% confidence interval level. Our preliminary findings suggested that CD151 may be involved in the estrogen responsive pathways. CD151 could be a potential prognostic marker and therapeutic target in the treatment of estrogen dependent breast cancer patients.
    Keywords:
    Breast carcinoma
    Hematology
    Oncologists now favor more personalized treatment strategies in breast cancer patients. Gene expression analysis has been widely used, but less is known about epigenetic factors, for example, microRNAs (miRNAs). The aim of this study was to determine the relationship between selected miRNAs and receptor status in core biopsies sampled before preoperative chemotherapy in stage III locally advanced breast cancer (LABC) patients. In 37 LABC core biopsies, three miRNAs per sample were analyzed: hsa-miR-93-5p, hsa-miR-190a, and hsa-miR-200b-3p, and hsa-miR-103a-3p as an endogenous control (TaqMan(®) RT-PCR; Applied Biosystems). Receptor status was determined by a dedicated pathologist. The Mann-Whitney U, Shapiro-Wilk, and Levene's tests were used to compare related samples. Levels of miRNA-93 differed significantly in core biopsies of LABC patients with different expressions of ER (estrogen receptor) and PR (progesterone receptor). Higher levels of miRNA-93 were found in ER-negative (p=0.0027) and PR-negative patients (p=0.0185). Levels of miRNA-190 and 200b did not differ significantly in core biopsies of LABC patients who expressed ER and PR differently (p=0.7727, p=0.9434, p=0.6213, and p=0.1717). Levels of miRNA-93, 190, and 200b were not significantly different in core biopsies of LABC patients with different HER2 (human epidermal growth factor 2) expressions (p=0.8013, p=0.2609, and p=0.3222). The assessment of core biopsy miRNA profiles and receptor-based subtypes may identify new signaling pathways for improved breast cancer classification.
    Progesterone receptor
    Citations (27)
    Objective To investigate the expression and clinical significance of the human kallikrein gene 8(KLK8) in human breast diseases.Methods We collected 61cases of breast cancer tissue and corresponding neighboring normal tissue,26 cases of breast fibroadenoma tissue were also collected in order to compared with the breast cancer tissue.The expression of KLK8 in breast cancer and neigboring tissues,and breast fibroadenoma and neigboring tissues were evaluated by quantitative real-time RT-PCR(qRT) and Western blotting methods.Results The KLK8 was downregulated in breast cancer tissue and is not found the phenomenon was not noted in fibroadenoma.The downregulation of the KLK8 was associated to primary cancer size,nodal status and tumor staging.Conclusions The KLK8 is downregulated in breast cancer and it could be a favorable tumor biomarker showing a better prognosis.
    Breast Fibroadenoma
    Clinical Significance
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    Abstract Background: Molecular characterization of Circulating Tumor Cells (CTC) can give important information on their suspected connection to cancer stem cells. In breast cancer, putative cancer stem cells have been identified to have a CD44+CD24-/low and ALDH1+ cell phenotype. Patients and methods: We developed a tetraplex quantitative RT-qPCR assay for CD24, CD44, ALDH1 and HPRT based on the in-silico design of primers and probes with different fluorescence emission spectra. Specificity and sensitivity experiments were performed using the SKBR-3 cancer cell line. We isolated CTC from peripheral blood according to our previously described methodology (Strati et al, BMC cancer 2011) from 40 patients with early breast cancer before the administration of adjuvant chemotherapy, 23 patients with verified metastasis and 18 female healthy volunteers. We evaluated all our data with respect to CD24, CD44, ALDH1 expression of healthy volunteers using the 2βΔΔCt method. Results: In 23 patients with verified metastasis 9.0% were found to have CD44+CD24-/low phenotype and 13% ALDH1high/CD24-/low phenotype. In 40 operable breast cancer patients 8 patients (20.0%) were found to have CD44+CD24-/low phenotype and 12 patients (30.0%) were found to have ALDH1high/CD24-/low phenotype. CK-19, MAGE-A3, HER-2, TWIST1, hTERT α+β+, and mammaglobin gene transcripts were also quantified in the same samples. Discussion: Molecular characterization of CTC has shown that in breast cancer patients CTCs are partly characterized by a putative stem cell phenotype. The clinical significance of these findings in early breast cancer remains to be elucidated when the clinical outcome of these patients is known. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-306. doi:1538-7445.AM2012-LB-306
    CD24
    Circulating tumor cell
    Multiplex
    Abstract BACKGROUND Real‐time quantitative RT‐PCR analysis of laser microdissected tissue is considered the most accurate technique for determining tissue gene expression. The discovery of estrogen receptor beta (ERβ) has focussed renewed interest on the role of estrogen receptors in prostate cancer, yet few studies have utilized the technique to analyze estrogen receptor gene expression in prostate cancer. METHODS Fresh tissue was obtained from 11 radical prostatectomy specimens and from 6 patients with benign prostate hyperplasia. Pure populations of benign and malignant prostate epithelium were laser microdissected, followed by RNA isolation and electrophoresis. Quantitative RT‐PCR was performed using primers for androgen receptor (AR), estrogen receptor beta (ERβ), estrogen receptor alpha (ERα), progesterone receptor (PGR) and prostate specific antigen (PSA), with normalization to two housekeeping genes. Differences in gene expression were analyzed using the Mann–Whitney U ‐test. Correlation coefficients were analyzed using Spearman's test. RESULTS Significant positive correlations were seen when AR and AR‐dependent PSA, and ERα and ERα‐dependent PGR were compared, indicating a representative population of RNA transcripts. ERβ gene expression was significantly over‐expressed in the cancer group compared with benign controls ( P < 0.01). In contrast, PGR expression was significantly down‐regulated in the cancer group ( P < 0.05). There were no significant differences in AR, ERα or PSA expression between the groups. This study represents the first to show an upregulation of ERβ gene expression in laser microdissected prostate cancer specimens. CONCLUSIONS In concert with recent studies the findings suggest differential production of ERβ splice variants, which may play important roles in the genesis of prostate cancer. Prostate 69: 810–819, 2009. © 2009 Wiley‐Liss, Inc.
    Estrogen receptor beta
    Estrogen receptor alpha
    Citations (28)
    Background: Breast cancer (BC) is one of the most common cancers among women and is the main cause of cancer-related mortalities in the female population. The main cause of BC is not fully understood yet; however, many genes have been identified as risk factors that increase susceptibility to this disease. Objectives: The aim of this study was to evaluate the expression of ABCC12 gene in patients with ductal breast carcinoma and its relationship with other biomarkers including estrogen receptor (ER), progesterone receptor (RP) and human epidermal growth factor receptor 2 (HER-2). Methods: This study included nine women diagnosed with ductal breast carcinoma as cases and five healthy women as controls. RNA extraction from breast tissue and cDNA synthesis were performed, and the expression of ABCC12 gene was evaluated using the real time polymerase chain reaction (PCR) method. After preparing formalin-fixed paraffin-embedded breast tissues, immunohistochemical evaluation of these samples and chromogenic in situ hybridization (CISH) of ER, PR and HER-2 were performed. Results: The obtained results showed that the expression of ABCC12 gene in all the breast cancer tissues was 3.74 times higher than in controls (P = 0.007). Also, the expression of ABCC12 gene increased by 3.94 times in luminal B (P = 0.002), 3.54 times in HER-2 (1+) (P = 0.0006), 3.86 times in ER (+) (P = 0.002) and 3.63 times in PR (+) (P = 0.0005). Conclusions: Our study showed that the evaluation of the ABCC12 gene expression as a one of multi-drug resistance protein members can be used as a prognostic factor to identify the stages of BC and its therapeutic approaches.
    CISH
    Breast carcinoma
    Citations (2)
    Objective To investigate the methylation-profile of promoter of p27 in breast cancer.Methods To examine the expression of p27 at proteinum and mRNA level by methods immunohistochemical staining,hybridization in situ and RT-PCR which were performed in breast cancer cells and 45 specimens of breast cancer.The methylation specific PCR was used to establish the methylation-profile of the promoter of p27 of breast cancer.Results The low p27 expression rate was 55.6%(25/45).High methylation of promoter of p27 was found in part of specimens of breast cancer.Conclusion Low p27 expression might be regulated by high methylation of promoter of p27of breast cancer.
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    Binding of estrogen to ERα induced tumor growth in most ERα-positive breast cancers.the aim of this study was to determine the expression of ERα in women with breast cancer. In this study cancerous and non-cancerous paraffinembedded tissues were collected. total RNA was extracted. cDNA was synthesized by reverse transcription reaction. gene expression Was measured by using Relative real time pcr reaction. Estrogen receptor alpha Is expressed in both cancerous and non cancerous breast tissues but its expression in cancerous tissues is more than noncancerouse tissues (3.5 times).statistical analysis showed that there is significant correlation between estrogen receptor alpha expression and Stage of disease (P=0.01).It also showed that there is significant correlation between estrogen receptor alpha expression and pationt's age (P=0.05). Determination of estrogen receptor alpha expression can offer valuable prognostic information for clinical management of patients with breast cancer.
    Estrogen receptor alpha
    Estrogen receptor beta
    Alpha (finance)
    Citations (1)
    The expression of the ras and c-erbB2 oncoproteins (p21 and p185, respectively), together with estrogen receptor (ER) and progesterone receptor (PgR) determination, has been retrospectively analyzed in 68 primary breast carcinomas and in 19 normal breast tissue samples. The aims of this study were: a) to explore the association between ras and c-erbB2 expression; b) to evaluate the relationship between ras and c-erbB2 expression and both steroid receptor status and the classical clinical and pathological parameters; and c) to compare two different methods for p185 determination. p185 and p21 were measured by enzyme immunoassay (EIA); p185 was also determined by Western blotting (WB); ER and PgR were assayed by radioligand binding assay. The highest value of p185 in benign breast lesions was used as the threshold to distinguish between positive and negative samples. With this threshold the c-erbB2 oncoprotein was overexpressed in 41.2% (with EIA) and in 50% (with WB) of cancer samples. The concordance rate between the two methods was 79.4. No significant association was found between p21 and p185 levels either in cancer or in normal breast tissue samples. Increasing levels of tumor p21 were associated with a shorter time to recurrence and overall survival. Increasing levels of p185 were associated with a significantly shorter time to recurrence (p185 EIA: p = 0.04, p185 WB: p = 0.029) and overall survival (p185 EIA: p = 0.04, p185 WB: p = 0.029).
    Concordance
    Progesterone receptor
    Breast cancer is the most frequent malignancy among females. In this study, we analyzed the expression pattern of a homeobox gene (HOXD10) in human invasive ductal breast cancer tissues and normal tissues. With the ACTB (β-actin) gene as a reference, HOXD10 was detected in 60 breast cancer tissues by using the quantitative real-time PCR (qPCR) method with the Relative Expression Software Tool (REST). We found that the HOXD10 expression level was significantly different between cancerous and normal tissues. Downregulation of the HOXD10 gene expression was examined in high-grade samples. Low-grade tissue showed no difference from the control group. HOXD10 expression was reduced in grade II breast carcinoma tissues. This data reveal that misexpression of the HOXD10 gene supports the development and involvement in breast cancer and may serve as a potential biomarker for the diagnosis of human ductal invasive breast carcinoma.
    Citations (20)
    Objective To investigate the expression and significance of extracellular matrix protein 1(ECM1) in breast cancer tissues at the mRNA and protein levels.To evaluate and compare ECM1 expression by real-time RT-PCR with immunohistochemistry(IHC) as diagnostic aids in breast cancer.Methods ECM1 expression was studied in normal breast tissues and breast cancer using real-time RT-PCR with immunohistochemistry(IHC) .The performance characteristics of ECM1 expression were examined with receiver operating characteristic curves and the resulting area under the curve.Results ECM1 was highly expressed in breast cancer,compared with normal breast tissues,both at the mRNA(P 0.01) and protein(P 0.01) levels.ECM1 expression by real-time RT-PCR and IHC methods was useful in identifying breast cancer(AUC = 0.834 and 0.773,respectively) .Conclusions ECM1 was over-expressed in breast cancer tissues.We confirm that ECM1 expression has potential utility as an independent diagnostic marker for breast cancer.
    Citations (0)