Elevated expression of LSD1 (Lysine-specific demethylase 1) during tumour progression from pre-invasive to invasive ductal carcinoma of the breast

BMC Clinical Pathology - Tập 12 - Trang 1-7 - 2012
Nuran Serce1, Annette Gnatzy1, Susanne Steiner1, Henning Lorenzen2, Jutta Kirfel1, Reinhard Buettner3
1Institute of Pathology, University of Bonn, Bonn, Germany
2Institute of Medical Biometrics, Informatics and Epidemiology, University of Bonn, Bonn, Germany
3Institute of Pathology, University of Cologne, Cologne, Germany

Tóm tắt

Lysine-specific demethylase1 (LSD1) is a nuclear protein which belongs to the aminooxidase-enzymes playing an important role in controlling gene expression. It has also been found highly expressed in several human malignancies including breast carcinoma. Our aim was to detect LSD1 expression also in pre-invasive neoplasias of the breast. In the current study we therefore analysed LSD1 protein expression in ductal carcinoma in situ (DCIS) in comparison to invasive ductal breast cancer (IDC). Using immunohistochemistry we systematically analysed LSD1 expression in low grade DCIS (n = 27), intermediate grade DCIS (n = 30), high grade DCIS (n = 31) and in invasive ductal breast cancer (n = 32). SPSS version 18.0 was used for statistical analysis. LSD1 was differentially expressed in DCIS and invasive ductal breast cancer. Interestingly, LSD1 was significantly overexpressed in high grade DCIS versus low grade DCIS. Differences in LSD1 expression levels were also statistically significant between low/intermediate DCIS and invasive ductal breast carcinoma. LSD1 is also expressed in pre-invasive neoplasias of the breast. Additionally, there is a gradual increase of LSD1 expression within tumour progression from pre-invasive DCIS to invasive ductal breast carcinoma. Therefore upregulation of LSD1 may be an early tumour promoting event.

Tài liệu tham khảo

Culhane JC, Cole P: LSD1 and the chemistry of histone demethylation. Chem Bio. 2007, 11: 561-568. Strahl BD, Allis CD: The language of covalent histone modification. Nature. 2000, 403: 41-45. 10.1038/47412. Lan F, Nottke AC, Shi Y: Mechanisms involved in the regulation of histone lysine demethylases. Curr Opin Cell Biol. 2008, 20 (3): 316-325. 10.1016/j.ceb.2008.03.004. Shi YJ, Matson C, Lan F, Iwase S, Baba T, Shi Y: Regulation of LSD1 histone demethylase activity by associated factors. Mol Cell. 2005, 19: 857-864. 10.1016/j.molcel.2005.08.027. Forneris F, Battaglioni E, Mattevi A, Binda C: New roles of flavoproteins in molecular cell biology: Histone demethylase LSD1 and chromatin. FEBS. 2009, 276: 4304-4312. 10.1111/j.1742-4658.2009.07142.x. Scoumanne A, Chen X: The lysine-specific demethylase 1 is required for cell proliferation in both p53-depended and –independend manners. J Biol Chem. 2007, 282: 15471-15478. 10.1074/jbc.M701023200. Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA, Shi Y: Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell. 2004, 119: 941-953. 10.1016/j.cell.2004.12.012. Metzger E, Imhof A, Patel D, Kahl P, Hoffmeyer K, Friedrichs N, Müller JM, Greschik H, Kirfel J, Ji S, Kunowska N, Beisenherz-Huss C, Günther T, Buettner R, Schüle R: Phosphorylation of histone H3T6 by PKCßI controls demethylation at histone H3K4. Nature. 2010, 464: 792-796. 10.1038/nature08839. Kahl P, Gullotti L, Heukamp LC, Wolf S, Friedrichs N, Vorreuther R, Solleder G, Bastian PJ, Ellinger J, Metzger E, Schüle R, Buettner R: Androgen receptor coactivators lysine-specific histone demethylase 1 and four and a half LIM domain protein 2 predict risk of prostate cancer recurrence. Cancer Res. 2006, 66 (23): 11341-11347. 10.1158/0008-5472.CAN-06-1570. Schulte JH, Lim S, Schramm A, Friedrichs N, Koster J, Versteeg R, Ora I, Pajtler K, Klein-Hitpass L, Kuhfittig-Kulle S, Metzger E, Schüle R, Eggert A, Buettner R, Kirfel J: Lysine-specific demethylase 1 is strongly expressed in poor differentiated neuroblastoma: implications for therapy. Cancer Res. 2009, 69: 2065-2071. Hayami S, Kelly JD, Cho HS, Yoshimatsu M, Unoki M, Tsunoda T, Field HI, Neal DE, Yamaue H, Ponder BA, Nakamura Y, Hamamoto R: Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers. International Journal of Cancer. 2011, 128 (3): 574-586. 10.1002/ijc.25349. Kauffmann EC, Robinson BD, Downes MJ, Powell LG, Lee MM, Scherr DS, Gudas LJ, Mongan NP: Role of androgen receptor and associated lysine-demethylase coregulators, LSD1 and JMJD2A, in localilzed and advanced human bladder cancer. Mol Carcinog. 2011, 50 (12): 931-944. 10.1002/mc.20758. Epub 2011 Mar 11. Lim S, Janzer A, Becker A, Zimmer A, Schüle R, Buettner R, Kirfel J: Lysine-specific demethylase 1 (LSD1) is highly expressed in ER-negative breast cancers and a biomarker predicting aggressive biology. Carcinogenesis. 2010, 31 (3): 512-520. 10.1093/carcin/bgp324. Cui X, Schiff R, Arpino G, Osborne CK, Lee AV: Biology of progesterone receptor loss in breast cancer and its implication for endocrine therapy. J Clin Oncol. 2005, 23 (30): 7721-7735. 10.1200/JCO.2005.09.004. Bradley C, van der Meer R, Roodi N, Yan H, Chandrasekharan MB, Sun ZW, Mernaugh RL, Parl FF: Carcinogen-induced alteration in normal human mammary epithelial cells. Carcinogenesis. 2007, 28 (10): 2184-2192. 10.1093/carcin/bgm100. Tavassoli FA, Devilee P:World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. 2003, IARC Press, Lyon, Remmele W, Stegner HE: Recommendation for uniform definition of an immunoreactive score (IRS) for immunhistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe. 1987, 8 (3): 138-140. Punglia RS, Burstein HJ, Weeks JC: Radiation therapy for ductal carcinoma in situ: a decision analysis. Cancer. 2012, 118 (3): 603-611. 10.1002/cncr.26293. Epub 2011 Jun 30. Boughey JC, Gonzalez RJ, Bonner E, Kuerer HM: Current treatment and clinical trial developments for ductal carcinoma in situ of the breast. Oncologist. 2007, 12 (11): 1276-1287. 10.1634/theoncologist.12-11-1276. Kuerer HM, Buzdar AU, Mittendorf EA, Esteva FJ, Lucci A, Vence LM, Radvanyi L, Meric-Bernstam F, Hunt KK, Symmans WF: Biologic and immunologic effects of preoperative trastuzumab for ductal carcinoma in situ of the breast. Cancer. 2011, 117 (1): 39-47. 10.1002/cncr.25399. Lidauvais JC, Hwang ES, Karliner L, Nápoles A, Stewart S, Bloom J, Kaplan CP: Adjuvant hormonal therapy use among women with ductal carcinoma in situ. J Womens Health (Larchmt). 2012, 21 (1): 35-42. 10.1089/jwh.2011.2773. Epub 2011 Sep 8 Zujewski JA, Harlan LC, Morrell DM, Stevens JL: Ductal carcinoma in situ: trends in treatment over time in the US. Breast Cancer Res Treat. 2011, 127 (1): 251-257. 10.1007/s10549-010-1198-z. Lee MG, Wynder C, Schmidt DM, McCafferty DG, Shiekhattar R: Histone H3 Lysine 4 Demethylation is a target of nonselective antidepressive medications. Chemistry and Biology. 2006, 13: 563-567. 10.1016/j.chembiol.2006.05.004. Sobin LH, Gospodarowicz MK, Wittekind C: UICC: TNM classification of malignant tumors. 2009, Wiley-Blackwell, Oxford, 7 The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6890/12/13/prepub