TMSB4Y is a candidate tumor suppressor on the Y chromosome and is deleted in male breast cancer
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Hong Yuen Wong1, Grace M. Wang1, Sarah Croessmann1, Daniel J. Zabransky1, David Chu1, Joseph P. Garay1, Justin Cidado1,6, Rory L. Cochran1, Julia A. Beaver1, Anita Aggarwal2,3,4, Min-Ling Liu2,4, Pedram Argani1, Alan Meeker1, Paula J. Hurley1, Josh Lauring1 and Ben Ho Park1,5
1 The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
2 Veterans Affairs Medical Center, Washington, DC, USA
3 The Georgetown University, Washington, DC, USA
4 George Washington University School of Medicine, Washington, DC, USA
5 The Whiting School of Engineering, Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA
6 Present address: Oncology iMED, AstraZeneca, Waltham, MA, USA
Ben Ho Park, email:
Keywords: male breast cancer, Y chromosome, TMSB4Y, tumor suppressor, cancer genetics
Received: November 30, 2015 Accepted: December 20, 2015 Published: December 23, 2015
Male breast cancer comprises less than 1% of breast cancer diagnoses. Although estrogen exposure has been causally linked to the development of female breast cancers, the etiology of male breast cancer is unclear. Here, we show via fluorescence in situ hybridization (FISH) and droplet digital PCR (ddPCR) that the Y chromosome was clonally lost at a frequency of ~16% (5/31) in two independent cohorts of male breast cancer patients. We also show somatic loss of the Y chromosome gene TMSB4Y in a male breast tumor, confirming prior reports of loss at this locus in male breast cancers. To further understand the function of TMSB4Y, we created inducible cell lines of TMSB4Y in the female human breast epithelial cell line MCF-10A. Expression of TMSB4Y resulted in aberrant cellular morphology and reduced cell proliferation, with a corresponding reduction in the fraction of metaphase cells. We further show that TMSB4Y interacts directly with β-actin, the main component of the actin cytoskeleton and a cell cycle modulator. Taken together, our results suggest that clonal loss of the Y chromosome may contribute to male breast carcinogenesis, and that the TMSB4Y gene has tumor suppressor properties.
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