1.Phenotypic heterogeneity of mutations in androgen receptor gene.
Singh RAJENDER ; Lalji SINGH ; Kumarasamy THANGARAJ
Asian Journal of Andrology 2007;9(2):147-179
Androgen receptor (AR) gene has been extensively studied in diverse clinical conditions. In addition to the point mutations, trinucleotide repeat (CAG and GGN) length polymorphisms have been an additional subject of interest and controversy among geneticists. The polymorphic variations in triplet repeats have been associated with a number of disorders, but at the same time contradictory findings have also been reported. Further, studies on the same disorder in different populations have generated different results. Therefore, combined analysis or review of the published studies has been of much value to extract information on the significance of variations in the gene in various clinical conditions. AR genetics has been reviewed extensively but until now review articles have focused on individual clinical categories such as androgen insensitivity, male infertility, prostate cancer, and so on. We have made the first effort to review most the aspects of AR genetics. The impact of androgens in various disorders and polymorphic variations in the AR gene is the main focus of this review. Additionally, the correlations observed in various studies have been discussed in the light of in vitro evidences available for the effect of AR gene variations on the action of androgens.
Androgen-Insensitivity Syndrome
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genetics
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physiopathology
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Bone Diseases, Metabolic
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genetics
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physiopathology
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Breast Neoplasms
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genetics
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physiopathology
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Cognition Disorders
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genetics
;
physiopathology
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Digestive System Diseases
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genetics
;
physiopathology
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Female
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Genital Neoplasms, Female
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genetics
;
physiopathology
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Genital Neoplasms, Male
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genetics
;
physiopathology
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Humans
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Infertility, Male
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genetics
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Male
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Muscular Atrophy, Spinal
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genetics
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physiopathology
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Phenotype
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Point Mutation
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Polycystic Ovary Syndrome
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genetics
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physiopathology
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Polymorphism, Genetic
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Pre-Eclampsia
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genetics
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physiopathology
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Pregnancy
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Receptors, Androgen
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genetics
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physiology
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Schizophrenia
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genetics
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physiopathology
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Testosterone
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deficiency
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Trinucleotide Repeats
2.Updates on genes related to breast cancer metastasis.
Bing-bing LIU ; Jia WEI ; Li FU
Chinese Journal of Pathology 2008;37(4):266-269
Acetyltransferases
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genetics
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Breast Neoplasms
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genetics
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Female
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GPI-Linked Proteins
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Gene Expression Regulation, Neoplastic
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genetics
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Humans
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Membrane Glycoproteins
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genetics
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Neoplasm Metastasis
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genetics
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physiopathology
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S100 Proteins
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genetics
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Transcription Factors
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genetics
3.Expression of MT-1 MMP, MMP2, MMP9 and TIMP2 mRNAs in Ductal Carcinoma in Situ and Invasive Ductal Carcinoma of the Breast.
Hee Jung KIM ; Chan il PARK ; Byeong Woo PARK ; Hy de LEE ; Woo Hee JUNG
Yonsei Medical Journal 2006;47(3):333-342
We investigated the expression of membrane type-1 (MT1)-MMP, MMP2, MMP9 and TIMP2 mRNAs and their roles in ductal carcinoma in situ (DCIS) and T1 and T2 invasive ductal carcinoma of the breast. We further compared these two types of carcinomas for differences in microvessel density, and expression of angiogenic factors and CD44std. MT1-MMP, MMP2, MMP9 and TIMP2 mRNA were expressed in both DCIS and invasive ductal carcinomas. Expression rates of MT1-MMP, MMP2, MMP9 and TIMP2 mRNAs were not statistically different between DCIS and invasive ductal carcinomas, nor did they differ statistically when grouped by tumor size, histologic grade or nuclear grade of invasive ductal carcinoma. Microvessel density and expression of VEGF and TGF-beta were not statistically different between DCIS and invasive ductal carcinoma. CD44std expression was significantly increased in DCIS compared to invasive ductal carcinoma (p < 0.05) and it was also significantly increased in lower clinical stage, histologic grade and nuclear grade of invasive ductal carcinoma (p < 0.05). Axillary node metastasis was significantly correlated with MT1-MMP mRNA, VEGF and TGF-beta expression (p < 0.05) and MT1-MMP mRNA was positively correlated with VEGF expression and TIMP2 mRNA (p < 0.05). In summary, patterns of MMP mRNA expression in DCIS and invasive ductal carcinoma suggest that the invasive potential of breast carcinoma is already achieved before morphologically overt invasive growth is observed. As MT1-MMP mRNA expression is significantly correlated with axillary nodal metastasis, it may be useful as a prognostic indicator of invasive ductal carcinoma. Considering the positive correlation of MT1-MMP mRNA and TIMP2mRNA expression, our finding supports a role for TIMP2 in tumor growth, as well as the utility of CD44std as a prognostic indicator of breast cancer.
Tissue Inhibitor of Metalloproteinase-2/genetics
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RNA, Messenger/metabolism
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Matrix Metalloproteinases, Membrane-Associated
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Matrix Metalloproteinases/*genetics
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Matrix Metalloproteinase 9/genetics
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Matrix Metalloproteinase 2/genetics
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Matrix Metalloproteinase 1/genetics
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Humans
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Gene Expression Regulation, Neoplastic
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Gene Expression Regulation, Enzymologic
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Female
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Carcinoma, Ductal, Breast/genetics/*physiopathology
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Carcinoma in Situ/genetics/*physiopathology
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Breast Neoplasms/genetics/*physiopathology
4.Expression of MT-1 MMP, MMP2, MMP9 and TIMP2 mRNAs in Ductal Carcinoma in Situ and Invasive Ductal Carcinoma of the Breast.
Hee Jung KIM ; Chan il PARK ; Byeong Woo PARK ; Hy de LEE ; Woo Hee JUNG
Yonsei Medical Journal 2006;47(3):333-342
We investigated the expression of membrane type-1 (MT1)-MMP, MMP2, MMP9 and TIMP2 mRNAs and their roles in ductal carcinoma in situ (DCIS) and T1 and T2 invasive ductal carcinoma of the breast. We further compared these two types of carcinomas for differences in microvessel density, and expression of angiogenic factors and CD44std. MT1-MMP, MMP2, MMP9 and TIMP2 mRNA were expressed in both DCIS and invasive ductal carcinomas. Expression rates of MT1-MMP, MMP2, MMP9 and TIMP2 mRNAs were not statistically different between DCIS and invasive ductal carcinomas, nor did they differ statistically when grouped by tumor size, histologic grade or nuclear grade of invasive ductal carcinoma. Microvessel density and expression of VEGF and TGF-beta were not statistically different between DCIS and invasive ductal carcinoma. CD44std expression was significantly increased in DCIS compared to invasive ductal carcinoma (p < 0.05) and it was also significantly increased in lower clinical stage, histologic grade and nuclear grade of invasive ductal carcinoma (p < 0.05). Axillary node metastasis was significantly correlated with MT1-MMP mRNA, VEGF and TGF-beta expression (p < 0.05) and MT1-MMP mRNA was positively correlated with VEGF expression and TIMP2 mRNA (p < 0.05). In summary, patterns of MMP mRNA expression in DCIS and invasive ductal carcinoma suggest that the invasive potential of breast carcinoma is already achieved before morphologically overt invasive growth is observed. As MT1-MMP mRNA expression is significantly correlated with axillary nodal metastasis, it may be useful as a prognostic indicator of invasive ductal carcinoma. Considering the positive correlation of MT1-MMP mRNA and TIMP2mRNA expression, our finding supports a role for TIMP2 in tumor growth, as well as the utility of CD44std as a prognostic indicator of breast cancer.
Tissue Inhibitor of Metalloproteinase-2/genetics
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RNA, Messenger/metabolism
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Matrix Metalloproteinases, Membrane-Associated
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Matrix Metalloproteinases/*genetics
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Matrix Metalloproteinase 9/genetics
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Matrix Metalloproteinase 2/genetics
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Matrix Metalloproteinase 1/genetics
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Humans
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Gene Expression Regulation, Neoplastic
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Gene Expression Regulation, Enzymologic
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Female
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Carcinoma, Ductal, Breast/genetics/*physiopathology
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Carcinoma in Situ/genetics/*physiopathology
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Breast Neoplasms/genetics/*physiopathology
5.Research on phytoestrogenic effect of formononetin.
Jie YU ; Piwen ZHAO ; Jianzhao NIU ; Jifeng WANG ; Yuankui CAO ; Qingxiu HAO
China Journal of Chinese Materia Medica 2010;35(22):3060-3064
OBJECTIVEResearch on the phytoestrogenic effect and its possible mechanism of formononetin.
METHODTo evaluate the estrogenic effect and mechanisms of formononetin through the test of its influence on proliferation and ER subtype expression of T47D cells.
RESULTThe proliferation rates of T47D cells treated with 1 x 10(-7) -1 x 10(-6) mol x L(-1) formononetin were not increased. On the influence of ICI182, 780, the proliferation rates of T47D cells treated with 1 x 10(-7) 1 x 10(-6) mol x L(-1) formononetin were decreased. Formonenetin could induce the augment of ERalpha expression significantly of T47D.
CONCLUSIONFormonenetin has phytoestrogenic effect Formonenetin can not accelerate ER(+) T47D cell proliferation. But the expression level of ERalpha subtype in T47D cells change significantly with certain concentrations of formonenetin.
Breast Neoplasms ; drug therapy ; genetics ; metabolism ; physiopathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Female ; Humans ; Isoflavones ; pharmacology ; Phytoestrogens ; pharmacology ; Receptors, Estrogen ; genetics ; metabolism
6.P27Kip1 expression and its prognostic implication in breast carcinoma: a meta-analysis.
Rui-lian XIE ; Xiao-xiang GUAN ; Long-bang CHEN ; Jing-hua WANG ; Jian-ling BAI ; Bao-li ZHU ; Xiao-jun ZHOU
Chinese Journal of Pathology 2008;37(2):92-98
To evaluate the relationship between p27Kip1 low expression in breast cancer and its prognostic implication in breast carcinoma patients. Methods All data that were associated with the study of the relationship between p27Kip1 and the prognosis for breast cancer was pooled from Cochrane library, PubMed, Embase and Medlinebase. The outcome was measured using the risk ratio (RR). Data pooling was performed by RevMan 4. 2. Results 6457 patients from 20 studies were included in this meta-analysis. RR estimate of overall survival (OS) for patients with low level p27Kip1 was 2.07 [1.66,2.60] (P<0.01). For disease free survival (DFS), the pooled RR was 1.27 [1.10,1.47] (P<0.05). The combined RR estimate of relapse free survival (RFS) for patients with low level of p27Kip1 was 1.49 [0.92, 2.42] (P >0.05). In patients with lymph node negative breast carcinoma, the combined RR for OS and RFS were 1.98 [1.34,2.91] (P <0.01) and 1.28 [0.45,3.65] (P > 0.05), respectively. Among the patients with lymph node positive breast carcinoma, the combined RR for OS and RFS was 1.92 [1.31, 2.82] (P=0.0009) and 1.35 [0.96,1.89] (P>0.05) respectively. Conclusions Low level of p27Kip1 appears to be an independent prognostic factor to OS and DFS of breast cancer patients but not to RFS. Additional studies with large patient number and widely accepted practical methods are required to derive the precise prognostic significance of p27Kip1 expression in breast cancer patients.
Biomarkers, Tumor
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analysis
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Breast Neoplasms
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diagnosis
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genetics
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metabolism
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pathology
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Carcinoma
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diagnosis
;
genetics
;
metabolism
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Cyclin-Dependent Kinase Inhibitor p27
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genetics
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metabolism
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Disease-Free Survival
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Female
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Gene Expression Regulation, Neoplastic
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genetics
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Humans
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Lymphatic Metastasis
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diagnosis
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physiopathology
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Neoplasm Staging
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methods
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Prognosis
7.Effect of curcumin in inducing apoptosis of MDA-MB-213 cells by activating endoplasmic reticulum stress.
Ri HONG ; Yong-Qiang WU ; Yue WU
China Journal of Chinese Materia Medica 2014;39(8):1495-1498
OBJECTIVETo explore the possible mechanism of curcumin in inducing the apoptosis of breast cancer cell MDA-MB-231.
METHODCurcumin of different concentrations at 0, 10 25, 50, 100, 150, 200 micromol x L(-1) were used to intervene breast cancer cells MDA-MB-231 for 24 hours. MTT was used to observe its effect on the proliferation of breast cancer cells. The flow cytometry was used to detect its effect on the cell apoptosis. The real-time quantitative PCR and Western blot was used to assess the expression levels of GRP78 and CHOP in breast cancer cells.
RESULTCurcumin could inhibit the proliferative ability of breast cancer cells by inducing them in a concentration-dependent manner. Curcumin could significantly increase the expression levels of GRP78 and CHOP in breast cancer cells.
CONCLUSIONCurcumin could induce the apoptosis of breast cancer cells MDA-MB-231 by activating endoplasmic reticulum stress.
Apoptosis ; drug effects ; Breast Neoplasms ; drug therapy ; genetics ; metabolism ; physiopathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Curcumin ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Endoplasmic Reticulum Stress ; drug effects ; Female ; Heat-Shock Proteins ; genetics ; metabolism ; Humans ; Transcription Factor CHOP ; genetics ; metabolism
8.Relationship and clinical significance of KiSS-1, nuclear factor kappa B (NF-kappaB), p50, and matrix metalloproteinase 9 expression in breast cancer.
Xue YI ; Chang-ying LI ; Su-hua ZHANG ; Xian-hua WANG ; Zhan-qing LI ; Fang YANG
Chinese Journal of Pathology 2008;37(4):238-242
OBJECTIVETo study the expression of KiSS-1, nuclear factor kappa B (NF-kappaB) p50 and matrix metalloproteinase 9 (MMP-9) in breast cancer tissue and the relationship with clinicpathological factors.
METHODSImmunohistochemical staining for KiSS-1, NF-KappaBp50, and MMP-9 protein was performed in 152 cases of human breast tissue [92 cases of BC, 30 cases of epithelial hyperplasia, and 30 cases of peritumoral breast tissue (PMT)] and 54 cases of axillary lymph node metastases. In-situ hybridization for KiSS-1 mRNA was done in 50 cases of breast cancer, and 20 cases of PMT.
RESULTS(1) The expression of KiSS-1 gene was significantly higher in well-differentiated breast cancer than in PMT, and this expression progressively decreased with decreasing degree of tumor differentiation, increasing pathological grade, TNM stage and the presence of lymph node metastases. The expression of KiSS-1 gene in lymph node metastasis was markedly lower than the corresponding primary tumor. There was correlation between the expression of KiSS-1 mRNA and KiSS-1 protein in breast cancer group. (2) The expression of NF-kappaKBp50 and MMP-9 increased progressively with decreasing degree of tumor differentiation, increasing TNM stage, large tumor size ( >2 cm) and the presence of lymph node metastases.
CONCLUSIONSThe expression of KiSS-1 protein showed negative correlation with that of NF-kappaBp50 and MMP-9 respectively. MMP-9 protein expression was positively correlated with NF-kappap50 protein expression. These suggest that the genes of KiSS-1, NF-kappaBp50 and MMP-9 could be involved in the progression and metastasis of breast cancer.
Breast Neoplasms ; metabolism ; pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Kisspeptins ; Lymphatic Metastasis ; physiopathology ; Matrix Metalloproteinase 9 ; genetics ; metabolism ; NF-kappa B ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Statistics as Topic ; Tumor Suppressor Proteins ; genetics ; metabolism
9.Geldanamycin inhibits proliferation and motility of human HER2/neu-overexpressing breast cancer cell line SKBr3.
Ke WANG ; Qing-Yong MA ; Yu REN ; Jian-Jun HE ; Wu-Ke CHEN
Journal of Southern Medical University 2007;27(10):1480-1484
OBJECTIVETo investigate the antitumor effect of a benzoquinone ansamycin antibiotic, geldanamycin (GA), against HER2 /neu tyrosine kinase-overexpressing human breast cancer cell line SKBr3.
METHODSTo evaluate the antitumor activity of GA, the degradation of HER2 /neu tyrosine kinase in GA-treated SKBr3 cells was analyzed by Western blotting, their proliferation assessed using MTT assay, and the cell cycle distribution identified by flow cytometry. RT-PCR and Real-time PCR were employed to detect cyclin D1 mRNA expression and cell culture inserts model was used to evaluate the motility of the cells.
RESULTSGA induced a dose- and time-dependent degradation of HER2 /neu tyrosine kinase and cell proliferation inhibition. GA treatment obviously decreased the survival rates of the cancer cells, leading also to a dose-dependent G(1) arrest. The antitumor effects of GA proved to be relevant with declined transcription of cyclin D1. The GA-treated cells also exhibited reduced motility.
CONCLUSIONGA can efficiently destabilize HER2 /neu tyrosine kinase and inhibit the proliferation and motility of human breast cancer cell line SKBr3 overexpressing HER2 /neu tyrosine kinase.
Anti-Bacterial Agents ; pharmacology ; Benzoquinones ; pharmacology ; Breast Neoplasms ; genetics ; metabolism ; physiopathology ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Down-Regulation ; Female ; Gene Expression ; drug effects ; Humans ; Lactams, Macrocyclic ; pharmacology ; Receptor, ErbB-2 ; genetics ; metabolism
10.Focal adhesion kinase expression and angiogenesis in breast carcinoma.
Journal of Southern Medical University 2007;27(9):1370-1373
OBJECTIVETo investigate the expression of focal adhesion kinase (FAK) in breast carcinoma tissues and its association with microvessel density (MVD), and explore the relationship between FAK-mediated cell signaling and angiogenesis in breast carcinoma.
METHODSFAK and CD34 expressions were examined by immunohistochemistry with SP method in 88 breast carcinoma tissues and 30 tissues of benign breast disease. The correlations of FAK protein expression with MVD marked with CD34 and clinicopathological parameters were analyzed in breast carcinoma.
RESULTSIn the 88 breast carcinomas, the positivity rate of FAK was 68.2% (60/88) with MVD of (34.52-/+13.11) /HPE, showing significant differences from those of the benign disease group (P<0.01). FAK expression and MVD in breast carcinoma tissues were positively related to tumor size, axillary lymph node metastasis and clinical stage (P<0.05), but not to the patients' age or histopathological grade of the tumors (P>0.05). In breast carcinoma, the expression of FAK was positively related to MVD (P<0.01).
CONCLUSIONSFAK protein expression and MVD are closely correlated with the invasion and metastasis of breast carcinoma. FAK expression can promote angiogenesis of breast carcinoma.
Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; genetics ; metabolism ; pathology ; physiopathology ; Cytoplasm ; metabolism ; Female ; Focal Adhesion Protein-Tyrosine Kinases ; metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Invasiveness ; genetics ; Neovascularization, Pathologic ; metabolism