期刊论文详细信息
Journal of Translational Medicine
Gadd45a levels in human breast cancer are hormone receptor dependent
Dan A Liebermann2  Barbara Hoffman2  Yajue Huang3  Alliric Willis1  Jennifer S Tront4 
[1] Department of Surgery, Philadelphia, USA;Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA 19140, USA;Department of Pathology and Laboratory Medicine, Philadelphia, USA;Fels Institute for Cancer Research and Molecular Biology, Philadelphia, USA
关键词: Hormone receptor;    Breast cancer;    Gadd45a;   
Others  :  827515
DOI  :  10.1186/1479-5876-11-131
 received in 2013-02-22, accepted in 2013-05-06,  发布年份 2013
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【 摘 要 】

Background

Gadd45a is a member of the Gadd45 family of genes that are known stress sensors. Gadd45a has been shown to serve as an effector in oncogenic stress in breast carcinogenesis in murine models. The present study was aimed at clarifying the expression of Gadd45a in human breast cancer and its correlation with clinicopathologic features.

Methods

The expression levels of Gadd45a in breast tissue samples of female breast surgery cases were examined by immunohistochemistry (IHC) using a Gadd45a antibody. Percent staining was determined and statistical analyses were applied to determine prognostic correlations.

Results

56 female breast surgery cases were studied: Normal (11), Luminal A (9), Luminal B (11), HER2+ (10), Triple Negative (15). There was a highly significant difference in percent Gadd45a staining between groups [Mean]: Normal 16.3%; Luminal A 65.3%; Luminal B 80.7%; HER2+ 40.5%; TN 32%, P < 0.001, ANOVA. Gadd45a IHC levels for Normal cases found 82% negative/low. Luminal A breast cancer cases were found to be 67% high. Luminal B breast cancers were 100% high. Her2+ cases were 50% negative/low. Triple Negative cases were 67% negative/low. This difference in distribution of Gadd45a levels across breast cancer receptor subtypes was significant, P = 0.0009.

Conclusions

Gadd45a levels are significantly associated with hormone receptor status in human breast cancer. Normal breast tissue displays low Gadd45a levels. High Gadd45a levels are associated with Luminal A and Luminal B subtypes. Absence of hormone receptors in Triple Negative subtype is associated with Negative/Low levels of Gadd45a. Further studies are indicated to elucidate the role of Gadd45a in breast cancer as a potential prognosticator or target for treatment.

【 授权许可】

   
2013 Tront et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]U.S. Cancer Statistics Working Group: United States Cancer Statistics: 1999–2008 Incidence and Mortality Web-based Report. Atlanta (GA): Department of Health and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute. 2012. Available at: http://www.cdc.gov/uscs webcite
  • [2]American Cancer Society: Cancer Facts and Figures 2012. Atlanta, GA: American Cancer Society; 2012.
  • [3]Greene MI: Breast cancer genes. Oncogene Reviews 2000, 19:2984-2989.
  • [4]Cretu A, Sha X, Tront J, Hoffman B, Liebermann DA: Stress sensor Gadd45 genes as therapeutic targets in cancer. Cancer Ther 2009, 7(A):268-276.
  • [5]Liebermann D, Hoffman B: MyD genes in negative growth control. Oncogene Reviews 1998, 17:3319-3330.
  • [6]Fornace A, Jackman J, Hollander M, Hoffman-Liebermann B, Liebermann D: Genotoxic stress response genes and growth arrest genes: gadd, MyD and other genes induced by treatments eliciting growth arrest. Ann NY Acad Of Sci 1992, 663:139-154.
  • [7]Carrier F, Georgel P, Pourquier P, Blake M, Kontny H, Antinore M: Gadd45, a p53-responsive stress protein, modifies DNA accessibility on damaged chromatin. MCB 1999, 19:1673-1685.
  • [8]Miki Y, Swensen J, Shattuck-Eidens J, Futreal P, Harshman K, Tavtigian S: A strong candidate for the breast and ovarian susceptibility gene BRCA1. Science 1994, 266:66.
  • [9]Tront J, Hoffman B, Liebermann D: Gadd45a suppresses ras-driven mammary tumorigenesis by activation of Jnk and p38 stress signaling resulting in apoptosis and senescence. Cancer Res 2006, 17:8448-8454.
  • [10]Tront J, Hoffman B, Liebermann D: Gadd45a functions as a promoter or suppressor of breast cancer dependent on the oncogenic stress. Cancer Res 2010, 70:9671-9681.
  • [11]Lakhani S, Ellis I, Schnitt S, Tan P, van de Vijver MJ: Pathology and Genetics Tumours of the Breast and Female Genital Organs. Lyon, France: IARC WHO Classification of Tumours, No 4 Ed. IARC Press; 2012.
  • [12]Edge S, Byrd D, Compton C, Fritz A, Greene F, Trotti A (Eds): AJCC Cancer Staging Manual 7th Ed. New York: Springer; 2010.
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