Abstract

The transcription factor GATA3 plays a significant role in mammary gland development and differentiation. We analyzed expression of GATA3 in breast cancer (BC) cell lines and clinical specimens from BC patients in Taiwan. Semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), quantitative real-time PCR were carried out to determine the mRNA level of GATA3 from 241 pairs of matched tumor and adjacent normal tissues from anonymous female donors. GATA3 immunohistochemistry (IHC) staining and H-score were performed (n = 25). Inducing and silencing of GATA3 were done by exposure MCF-7 cell line to nicotine or curcumin, respectively. GATA3 expression was detected in most of the estrogen receptor–positive (ER+) tumor specimens (176/241, 73%) compared with paired normal tissues (65/241, 27%) (P <.001). The GATA3 level was highest in Luminal A, and independent t-tests revealed higher GATA3 was associated with ER+ (P =.018) and BC stages (stage II, and stage IV). Nuclear protein expression of GATA3 was detected in tumor tissues (P <.001) with higher H-score in Luminal A patients (P =.012). Kaplan–Meier survival analyses showed that ER+/progesterone receptor (PgR)+ and lower grade BC patients with relatively high GATA3 had better clinical overall survival (OS). GATA3 regulates ERα and BCL-2 as BC luminal subtype markers. Cox univariate and multivariate analyses demonstrated that the expression of GATA3 was an effective predictor of the risk of death. We demonstrated a correlation between GATA3 expression and only ER+ and suggest that a higher GATA3 expression is a good prognostic factor for OS for ER+ BC patients. © 2018 Elsevier Inc.
Original languageEnglish
Pages (from-to)219-230
Number of pages12
JournalHuman Pathology
Volume80
DOIs
Publication statusPublished - 2018

Fingerprint

Breast Neoplasms
GATA3 Transcription Factor
Cell Line
Neoplasms
Curcumin
Survival
MCF-7 Cells
Progesterone Receptors
Human Mammary Glands
Survival Analysis
Nuclear Proteins
Taiwan
Nicotine
Reverse Transcription
Real-Time Polymerase Chain Reaction
Estrogens
Multivariate Analysis
Immunohistochemistry
Tissue Donors
Staining and Labeling

Keywords

  • Breast cancer
  • Estrogen receptor
  • GATA3
  • Overall survival
  • Prognostic factor
  • messenger RNA
  • nuclear protein
  • protein bcl 2
  • tamoxifen
  • transcription factor GATA 3
  • trastuzumab
  • adult
  • Article
  • breast cancer
  • cancer chemotherapy
  • cancer mortality
  • cancer patient
  • cancer prognosis
  • cancer radiotherapy
  • cancer survival
  • comparative study
  • estrogen receptor negative breast cancer
  • estrogen receptor positive breast cancer
  • gene silencing
  • human
  • human cell
  • human epidermal growth factor receptor 2 positive breast cancer
  • human tissue
  • immunohistochemistry
  • luminal A breast cancer
  • major clinical study
  • MCF-7 cell line
  • mRNA expression level
  • overall survival
  • progesterone receptor positive breast cancer
  • protein localization
  • quantitative analysis
  • real time polymerase chain reaction
  • reverse transcription polymerase chain reaction
  • Taiwan

Cite this

The impact of the effectiveness of GATA3 as a prognostic factor in breast cancer. / Fararjeh, A.-F.S.; Tu, S.-H.; Chen, L.-C.; Liu, Y.-R.; Lin, Y.-K.; Chang, H.-L.; Chang, H.-W.; Wu, C.-H.; Hwang-Verslues, W.W.; Ho, Y.-S.

In: Human Pathology, Vol. 80, 2018, p. 219-230.

Research output: Contribution to journalArticle

Fararjeh, A.-F.S. ; Tu, S.-H. ; Chen, L.-C. ; Liu, Y.-R. ; Lin, Y.-K. ; Chang, H.-L. ; Chang, H.-W. ; Wu, C.-H. ; Hwang-Verslues, W.W. ; Ho, Y.-S. / The impact of the effectiveness of GATA3 as a prognostic factor in breast cancer. In: Human Pathology. 2018 ; Vol. 80. pp. 219-230.
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title = "The impact of the effectiveness of GATA3 as a prognostic factor in breast cancer",
abstract = "The transcription factor GATA3 plays a significant role in mammary gland development and differentiation. We analyzed expression of GATA3 in breast cancer (BC) cell lines and clinical specimens from BC patients in Taiwan. Semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), quantitative real-time PCR were carried out to determine the mRNA level of GATA3 from 241 pairs of matched tumor and adjacent normal tissues from anonymous female donors. GATA3 immunohistochemistry (IHC) staining and H-score were performed (n = 25). Inducing and silencing of GATA3 were done by exposure MCF-7 cell line to nicotine or curcumin, respectively. GATA3 expression was detected in most of the estrogen receptor–positive (ER+) tumor specimens (176/241, 73{\%}) compared with paired normal tissues (65/241, 27{\%}) (P <.001). The GATA3 level was highest in Luminal A, and independent t-tests revealed higher GATA3 was associated with ER+ (P =.018) and BC stages (stage II, and stage IV). Nuclear protein expression of GATA3 was detected in tumor tissues (P <.001) with higher H-score in Luminal A patients (P =.012). Kaplan–Meier survival analyses showed that ER+/progesterone receptor (PgR)+ and lower grade BC patients with relatively high GATA3 had better clinical overall survival (OS). GATA3 regulates ERα and BCL-2 as BC luminal subtype markers. Cox univariate and multivariate analyses demonstrated that the expression of GATA3 was an effective predictor of the risk of death. We demonstrated a correlation between GATA3 expression and only ER+ and suggest that a higher GATA3 expression is a good prognostic factor for OS for ER+ BC patients. {\circledC} 2018 Elsevier Inc.",
keywords = "Breast cancer, Estrogen receptor, GATA3, Overall survival, Prognostic factor, messenger RNA, nuclear protein, protein bcl 2, tamoxifen, transcription factor GATA 3, trastuzumab, adult, Article, breast cancer, cancer chemotherapy, cancer mortality, cancer patient, cancer prognosis, cancer radiotherapy, cancer survival, comparative study, estrogen receptor negative breast cancer, estrogen receptor positive breast cancer, gene silencing, human, human cell, human epidermal growth factor receptor 2 positive breast cancer, human tissue, immunohistochemistry, luminal A breast cancer, major clinical study, MCF-7 cell line, mRNA expression level, overall survival, progesterone receptor positive breast cancer, protein localization, quantitative analysis, real time polymerase chain reaction, reverse transcription polymerase chain reaction, Taiwan",
author = "A.-F.S. Fararjeh and S.-H. Tu and L.-C. Chen and Y.-R. Liu and Y.-K. Lin and H.-L. Chang and H.-W. Chang and C.-H. Wu and W.W. Hwang-Verslues and Y.-S. Ho",
note = "Export Date: 17 October 2018 CODEN: HPCQA Correspondence Address: Ho, Y.-S.; Graduate Institute of Medical Science, College of Medicine, Taipei Medical University, No. 250 Wu-Hsing street, Taiwan; email: hoyuansn@tmu.edu.tw Chemicals/CAS: protein bcl 2, 219306-68-0; tamoxifen, 10540-29-1; transcription factor GATA 3, 137878-55-8; trastuzumab, 180288-69-1, 1446410-98-5 Funding details: Ministry of Education Funding details: MOST106-2314-B-038-053-MY3, MOST, Ministry of Science and Technology, Taiwan Funding details: MOST104-2314-B-038-059-MY3, MOST, Ministry of Science and Technology, Taiwan Funding details: MOST105-2320-B-038-053-MY3, MOST, Ministry of Science and Technology, Taiwan Funding details: MOST106-2320-B-038-046, MOST, Ministry of Science and Technology, Taiwan Funding details: 106-2320-B-038-061 -MY3, MOST, Ministry of Science and Technology, Taiwan Funding details: MOHW107-TDU-B-212-114014 Funding details: MOE, Ministry of Education - Singapore Funding text: This study was supported by the Health and Welfare surcharge of tobacco products grant (MOHW107-TDU-B-212-114014), by TMU Research Center of Cancer Translational Medicine from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan and by the Ministry of Science and Technology, Taiwan (MOST105-2320-B-038-053-MY3 and MOST106-2320-B-038-046 awarded to Dr. Ho, MOST106-2314-B-038-053-MY3 awarded to Dr. Tu, MOST 106-2320-B-038-061 -MY3 awarded to Dr. Chen, and MOST104-2314-B-038-059-MY3 awarded to Dr. Wu). References: Ferlay, J., Soerjomataram, I., Dikshit, R., Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012 (2015) Int J Cancer, 136, pp. E359-E386; Small, E.J., Schellhammer, P.F., Higano, C.S., Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer (2006) J Clin Oncol, 24, pp. 3089-3094; Halabi, S., Owzar, K., The importance of identifying and validating prognostic factors in oncology (2010) Semin Oncol, 37, pp. e9-e18; Joe, S., Nam, H., Prognostic factor analysis for breast cancer using gene expression profiles (2016) BMC Med Inform Decis Mak; Zheng, R., Blobel, G.A., GATA Transcription factors and cancer (2010) Genes Cancer, 1, pp. 1178-1188; Zheng, W.P., Flavell, R.A., The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells (2016) J Immunol, 196, pp. 4426-4435; Yagi, R., Zhu, J.F., Paul, W.E., An updated view on transcription factor GATA3-mediated regulation of T(h)1 and T(h)2 cell differentiation (2011) Int Immunol, 23, pp. 415-420; Zhou, M., Ouyang, W., The function role of GATA-3 in Th1 and Th2 differentiation (2003) Immunol Res, 28, pp. 25-37; Asselin-Labat, M.L., Sutherland, K.D., Barker, H., Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation (2007) Nat Cell Biol, 9; Yan, W., Cao, Q.J., Arenas, R.B., Bentley, B., Shao, R., GATA3 inhibits breast cancer metastasis through the reversal of epithelial-mesenchymal transition (2010) J Biol Chem, 285, pp. 14042-14051; Yu, K.D., Zhu, R., Zhan, M., Identification of prognosis-relevant subgroups in patients with chemoresistant triple-negative breast cancer (2013) Clin Cancer Res, 19, pp. 2723-2733; Liu, H., Shi, J., Wilkerson, M.L., Lin, F., Immunohistochemical evaluation of GATA3 expression in tumors and normal tissues: a useful immunomarker for breast and urothelial carcinomas (2012) Am J Clin Pathol, 138, pp. 57-64; Miettinen, M., McCue, P.A., Sarlomo-Rikala, M., GATA3: a multispecific but potentially useful marker in surgical pathology: a systematic analysis of 2500 epithelial and nonepithelial tumors (2014) Am J Surg Pathol, 38, pp. 13-22; Yang, M., Nonaka, D., A study of immunohistochemical differential expression in pulmonary and mammary carcinomas (2010) Mod Pathol, 23, pp. 654-661; Cimino-Mathews, A., Subhawong, A.P., Illei, P.B., GATA3 expression in breast carcinoma: utility in triple-negative, sarcomatoid, and metastatic carcinomas (2013) HUM PATHOL, 44, pp. 1341-1349; Mehra, R., Varambally, S., Ding, L., Identification of GATA3 as a breast cancer prognostic marker by global gene expression meta-analysis (2005) Cancer Res, 65, pp. 11259-11264; Albergaria, A., Paredes, J., Sousa, B., Expression of FOXA1 and GATA-3 in breast cancer: the prognostic significance in hormone receptor-negative tumours (2009) Breast Cancer Res, 11; Theodorou, V., Stark, R., Menon, S., Carroll, J.S., GATA3 acts upstream of FOXA1 in mediating ESR1 binding by shaping enhancer accessibility (2013) Genome Res, 23, pp. 12-22; Cohen, H., Ben-Hamo, R., Gidoni, M., Shift in GATA3 functions, and GATA3 mutations, control progression and clinical presentation in breast cancer (2014) Breast Cancer Res, 16, p. 464; Cheng, T.C., Tu, S.H., Chen, L.C., Down-regulation of alpha-L-fucosidase 1 expression confers inferior survival for triple-negative breast cancer patients by modulating the glycosylation status of the tumor cell surface (2015) Oncotarget, 6, pp. 21283-21300; Liu, J., Prager-van der Smissen, W.J., Look, M.P., GATA3 mRNA expression, but not mutation, associates with longer progression-free survival in ER-positive breast cancer patients treated with first-line tamoxifen for recurrent disease (2016) Cancer Lett, 376, pp. 104-109; Paolicchi, E., Crea, F., Farrar, W.L., Green, J.E., Danesi, R., Histone lysine demethylases in breast cancer (2013) Crit Rev Oncol Hematol; Voduc, D., Cheang, M., Nielsen, T., GATA-3 expression in breast cancer has a strong association with estrogen receptor but lacks independent prognostic value (2008) Cancer Epidemiol Biomark Prev, 17, pp. 365-373; Yoon, N.K., Maresh, E.L., Shen, D.J., Higher levels of GATA3 predict better survival in women with breast cancer (2010) HUM PATHOL, 41, pp. 1794-1801; Hallman, K., Aleck, K., Dwyer, B., The effects of turmeric (curcumin) on tumor suppressor protein (p53) and estrogen receptor (ERalpha) in breast cancer cells (2017) Breast Cancer (Dove Med Press), 9, pp. 153-161; Inman, D., Kawana, K., Schust, D., Lininger, R., Young, S., Cyclic regulation of T-Bet and GATA-3 in human endometrium (2008) Reprod Sci, 15, pp. 83-90; Tominaga, N., Naoi, Y., Shimazu, K., Clinicopathological analysis of GATA3-positive breast cancers with special reference to response to neoadjuvant chemotherapy (2012) Ann Oncol, 23, pp. 3051-3057; Bertucci, F., Houlgatte, R., Benziane, A., Gene expression profiling of primary breast carcinomas using arrays of candidate genes (2000) Hum Mol Genet, 9, pp. 2981-2991; Jenssen, T.K., Kuo, W.P., Stokke, T., Hovig, E., Associations between gene expressions in breast cancer and patient survival (2002) Hum Genet, 111, pp. 411-420; Martin, L.A., Dowsett, M., BCL-2: a new therapeutic target in estrogen receptor-positive breast cancer? (2013) Cancer Cell, 24, pp. 7-9; Kikuchi, H., Itoh, J., Fukuda, S., Chronic nicotine stimulation modulates the immune response of mucosal T cells to Th1-dominant pattern via nAChR by upregulation of Th1-specific transcriptional factor (2008) Neurosci Lett, 432, pp. 217-221; Lee, C.H., Huang, C.S., Chen, C.S., Overexpression and activation of the alpha9-nicotinic receptor during tumorigenesis in human breast epithelial cells (2010) J Natl Cancer Inst, 102, pp. 1322-1335; Eeckhoute, J., Keeton, E.K., Lupien, M., Krum, S.A., Carroll, J.S., Brown, M., Positive cross-regulatory loop ties GATA-3 to estrogen receptor alpha expression in breast cancer (2007) Cancer Res, 67, pp. 6477-6483; Usary, J., Llaca, V., Karaca, G., Mutation of GATA3 in human breast tumors (2004) Oncogene, 23, pp. 7669-7678",
year = "2018",
doi = "10.1016/j.humpath.2018.06.004",
language = "English",
volume = "80",
pages = "219--230",
journal = "Human Pathology",
issn = "0046-8177",
publisher = "W.B. Saunders",

}

TY - JOUR

T1 - The impact of the effectiveness of GATA3 as a prognostic factor in breast cancer

AU - Fararjeh, A.-F.S.

AU - Tu, S.-H.

AU - Chen, L.-C.

AU - Liu, Y.-R.

AU - Lin, Y.-K.

AU - Chang, H.-L.

AU - Chang, H.-W.

AU - Wu, C.-H.

AU - Hwang-Verslues, W.W.

AU - Ho, Y.-S.

N1 - Export Date: 17 October 2018 CODEN: HPCQA Correspondence Address: Ho, Y.-S.; Graduate Institute of Medical Science, College of Medicine, Taipei Medical University, No. 250 Wu-Hsing street, Taiwan; email: hoyuansn@tmu.edu.tw Chemicals/CAS: protein bcl 2, 219306-68-0; tamoxifen, 10540-29-1; transcription factor GATA 3, 137878-55-8; trastuzumab, 180288-69-1, 1446410-98-5 Funding details: Ministry of Education Funding details: MOST106-2314-B-038-053-MY3, MOST, Ministry of Science and Technology, Taiwan Funding details: MOST104-2314-B-038-059-MY3, MOST, Ministry of Science and Technology, Taiwan Funding details: MOST105-2320-B-038-053-MY3, MOST, Ministry of Science and Technology, Taiwan Funding details: MOST106-2320-B-038-046, MOST, Ministry of Science and Technology, Taiwan Funding details: 106-2320-B-038-061 -MY3, MOST, Ministry of Science and Technology, Taiwan Funding details: MOHW107-TDU-B-212-114014 Funding details: MOE, Ministry of Education - Singapore Funding text: This study was supported by the Health and Welfare surcharge of tobacco products grant (MOHW107-TDU-B-212-114014), by TMU Research Center of Cancer Translational Medicine from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan and by the Ministry of Science and Technology, Taiwan (MOST105-2320-B-038-053-MY3 and MOST106-2320-B-038-046 awarded to Dr. Ho, MOST106-2314-B-038-053-MY3 awarded to Dr. Tu, MOST 106-2320-B-038-061 -MY3 awarded to Dr. Chen, and MOST104-2314-B-038-059-MY3 awarded to Dr. Wu). References: Ferlay, J., Soerjomataram, I., Dikshit, R., Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012 (2015) Int J Cancer, 136, pp. E359-E386; Small, E.J., Schellhammer, P.F., Higano, C.S., Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer (2006) J Clin Oncol, 24, pp. 3089-3094; Halabi, S., Owzar, K., The importance of identifying and validating prognostic factors in oncology (2010) Semin Oncol, 37, pp. e9-e18; Joe, S., Nam, H., Prognostic factor analysis for breast cancer using gene expression profiles (2016) BMC Med Inform Decis Mak; Zheng, R., Blobel, G.A., GATA Transcription factors and cancer (2010) Genes Cancer, 1, pp. 1178-1188; Zheng, W.P., Flavell, R.A., The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells (2016) J Immunol, 196, pp. 4426-4435; Yagi, R., Zhu, J.F., Paul, W.E., An updated view on transcription factor GATA3-mediated regulation of T(h)1 and T(h)2 cell differentiation (2011) Int Immunol, 23, pp. 415-420; Zhou, M., Ouyang, W., The function role of GATA-3 in Th1 and Th2 differentiation (2003) Immunol Res, 28, pp. 25-37; Asselin-Labat, M.L., Sutherland, K.D., Barker, H., Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation (2007) Nat Cell Biol, 9; Yan, W., Cao, Q.J., Arenas, R.B., Bentley, B., Shao, R., GATA3 inhibits breast cancer metastasis through the reversal of epithelial-mesenchymal transition (2010) J Biol Chem, 285, pp. 14042-14051; Yu, K.D., Zhu, R., Zhan, M., Identification of prognosis-relevant subgroups in patients with chemoresistant triple-negative breast cancer (2013) Clin Cancer Res, 19, pp. 2723-2733; Liu, H., Shi, J., Wilkerson, M.L., Lin, F., Immunohistochemical evaluation of GATA3 expression in tumors and normal tissues: a useful immunomarker for breast and urothelial carcinomas (2012) Am J Clin Pathol, 138, pp. 57-64; Miettinen, M., McCue, P.A., Sarlomo-Rikala, M., GATA3: a multispecific but potentially useful marker in surgical pathology: a systematic analysis of 2500 epithelial and nonepithelial tumors (2014) Am J Surg Pathol, 38, pp. 13-22; Yang, M., Nonaka, D., A study of immunohistochemical differential expression in pulmonary and mammary carcinomas (2010) Mod Pathol, 23, pp. 654-661; Cimino-Mathews, A., Subhawong, A.P., Illei, P.B., GATA3 expression in breast carcinoma: utility in triple-negative, sarcomatoid, and metastatic carcinomas (2013) HUM PATHOL, 44, pp. 1341-1349; Mehra, R., Varambally, S., Ding, L., Identification of GATA3 as a breast cancer prognostic marker by global gene expression meta-analysis (2005) Cancer Res, 65, pp. 11259-11264; Albergaria, A., Paredes, J., Sousa, B., Expression of FOXA1 and GATA-3 in breast cancer: the prognostic significance in hormone receptor-negative tumours (2009) Breast Cancer Res, 11; Theodorou, V., Stark, R., Menon, S., Carroll, J.S., GATA3 acts upstream of FOXA1 in mediating ESR1 binding by shaping enhancer accessibility (2013) Genome Res, 23, pp. 12-22; Cohen, H., Ben-Hamo, R., Gidoni, M., Shift in GATA3 functions, and GATA3 mutations, control progression and clinical presentation in breast cancer (2014) Breast Cancer Res, 16, p. 464; Cheng, T.C., Tu, S.H., Chen, L.C., Down-regulation of alpha-L-fucosidase 1 expression confers inferior survival for triple-negative breast cancer patients by modulating the glycosylation status of the tumor cell surface (2015) Oncotarget, 6, pp. 21283-21300; Liu, J., Prager-van der Smissen, W.J., Look, M.P., GATA3 mRNA expression, but not mutation, associates with longer progression-free survival in ER-positive breast cancer patients treated with first-line tamoxifen for recurrent disease (2016) Cancer Lett, 376, pp. 104-109; Paolicchi, E., Crea, F., Farrar, W.L., Green, J.E., Danesi, R., Histone lysine demethylases in breast cancer (2013) Crit Rev Oncol Hematol; Voduc, D., Cheang, M., Nielsen, T., GATA-3 expression in breast cancer has a strong association with estrogen receptor but lacks independent prognostic value (2008) Cancer Epidemiol Biomark Prev, 17, pp. 365-373; Yoon, N.K., Maresh, E.L., Shen, D.J., Higher levels of GATA3 predict better survival in women with breast cancer (2010) HUM PATHOL, 41, pp. 1794-1801; Hallman, K., Aleck, K., Dwyer, B., The effects of turmeric (curcumin) on tumor suppressor protein (p53) and estrogen receptor (ERalpha) in breast cancer cells (2017) Breast Cancer (Dove Med Press), 9, pp. 153-161; Inman, D., Kawana, K., Schust, D., Lininger, R., Young, S., Cyclic regulation of T-Bet and GATA-3 in human endometrium (2008) Reprod Sci, 15, pp. 83-90; Tominaga, N., Naoi, Y., Shimazu, K., Clinicopathological analysis of GATA3-positive breast cancers with special reference to response to neoadjuvant chemotherapy (2012) Ann Oncol, 23, pp. 3051-3057; Bertucci, F., Houlgatte, R., Benziane, A., Gene expression profiling of primary breast carcinomas using arrays of candidate genes (2000) Hum Mol Genet, 9, pp. 2981-2991; Jenssen, T.K., Kuo, W.P., Stokke, T., Hovig, E., Associations between gene expressions in breast cancer and patient survival (2002) Hum Genet, 111, pp. 411-420; Martin, L.A., Dowsett, M., BCL-2: a new therapeutic target in estrogen receptor-positive breast cancer? (2013) Cancer Cell, 24, pp. 7-9; Kikuchi, H., Itoh, J., Fukuda, S., Chronic nicotine stimulation modulates the immune response of mucosal T cells to Th1-dominant pattern via nAChR by upregulation of Th1-specific transcriptional factor (2008) Neurosci Lett, 432, pp. 217-221; Lee, C.H., Huang, C.S., Chen, C.S., Overexpression and activation of the alpha9-nicotinic receptor during tumorigenesis in human breast epithelial cells (2010) J Natl Cancer Inst, 102, pp. 1322-1335; Eeckhoute, J., Keeton, E.K., Lupien, M., Krum, S.A., Carroll, J.S., Brown, M., Positive cross-regulatory loop ties GATA-3 to estrogen receptor alpha expression in breast cancer (2007) Cancer Res, 67, pp. 6477-6483; Usary, J., Llaca, V., Karaca, G., Mutation of GATA3 in human breast tumors (2004) Oncogene, 23, pp. 7669-7678

PY - 2018

Y1 - 2018

N2 - The transcription factor GATA3 plays a significant role in mammary gland development and differentiation. We analyzed expression of GATA3 in breast cancer (BC) cell lines and clinical specimens from BC patients in Taiwan. Semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), quantitative real-time PCR were carried out to determine the mRNA level of GATA3 from 241 pairs of matched tumor and adjacent normal tissues from anonymous female donors. GATA3 immunohistochemistry (IHC) staining and H-score were performed (n = 25). Inducing and silencing of GATA3 were done by exposure MCF-7 cell line to nicotine or curcumin, respectively. GATA3 expression was detected in most of the estrogen receptor–positive (ER+) tumor specimens (176/241, 73%) compared with paired normal tissues (65/241, 27%) (P <.001). The GATA3 level was highest in Luminal A, and independent t-tests revealed higher GATA3 was associated with ER+ (P =.018) and BC stages (stage II, and stage IV). Nuclear protein expression of GATA3 was detected in tumor tissues (P <.001) with higher H-score in Luminal A patients (P =.012). Kaplan–Meier survival analyses showed that ER+/progesterone receptor (PgR)+ and lower grade BC patients with relatively high GATA3 had better clinical overall survival (OS). GATA3 regulates ERα and BCL-2 as BC luminal subtype markers. Cox univariate and multivariate analyses demonstrated that the expression of GATA3 was an effective predictor of the risk of death. We demonstrated a correlation between GATA3 expression and only ER+ and suggest that a higher GATA3 expression is a good prognostic factor for OS for ER+ BC patients. © 2018 Elsevier Inc.

AB - The transcription factor GATA3 plays a significant role in mammary gland development and differentiation. We analyzed expression of GATA3 in breast cancer (BC) cell lines and clinical specimens from BC patients in Taiwan. Semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), quantitative real-time PCR were carried out to determine the mRNA level of GATA3 from 241 pairs of matched tumor and adjacent normal tissues from anonymous female donors. GATA3 immunohistochemistry (IHC) staining and H-score were performed (n = 25). Inducing and silencing of GATA3 were done by exposure MCF-7 cell line to nicotine or curcumin, respectively. GATA3 expression was detected in most of the estrogen receptor–positive (ER+) tumor specimens (176/241, 73%) compared with paired normal tissues (65/241, 27%) (P <.001). The GATA3 level was highest in Luminal A, and independent t-tests revealed higher GATA3 was associated with ER+ (P =.018) and BC stages (stage II, and stage IV). Nuclear protein expression of GATA3 was detected in tumor tissues (P <.001) with higher H-score in Luminal A patients (P =.012). Kaplan–Meier survival analyses showed that ER+/progesterone receptor (PgR)+ and lower grade BC patients with relatively high GATA3 had better clinical overall survival (OS). GATA3 regulates ERα and BCL-2 as BC luminal subtype markers. Cox univariate and multivariate analyses demonstrated that the expression of GATA3 was an effective predictor of the risk of death. We demonstrated a correlation between GATA3 expression and only ER+ and suggest that a higher GATA3 expression is a good prognostic factor for OS for ER+ BC patients. © 2018 Elsevier Inc.

KW - Breast cancer

KW - Estrogen receptor

KW - GATA3

KW - Overall survival

KW - Prognostic factor

KW - messenger RNA

KW - nuclear protein

KW - protein bcl 2

KW - tamoxifen

KW - transcription factor GATA 3

KW - trastuzumab

KW - adult

KW - Article

KW - breast cancer

KW - cancer chemotherapy

KW - cancer mortality

KW - cancer patient

KW - cancer prognosis

KW - cancer radiotherapy

KW - cancer survival

KW - comparative study

KW - estrogen receptor negative breast cancer

KW - estrogen receptor positive breast cancer

KW - gene silencing

KW - human

KW - human cell

KW - human epidermal growth factor receptor 2 positive breast cancer

KW - human tissue

KW - immunohistochemistry

KW - luminal A breast cancer

KW - major clinical study

KW - MCF-7 cell line

KW - mRNA expression level

KW - overall survival

KW - progesterone receptor positive breast cancer

KW - protein localization

KW - quantitative analysis

KW - real time polymerase chain reaction

KW - reverse transcription polymerase chain reaction

KW - Taiwan

U2 - 10.1016/j.humpath.2018.06.004

DO - 10.1016/j.humpath.2018.06.004

M3 - Article

VL - 80

SP - 219

EP - 230

JO - Human Pathology

JF - Human Pathology

SN - 0046-8177

ER -