TMSB4Y is a candidate tumor suppressor on the Y chromosome and is deleted in male breast cancer.

Abstract

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.

• Authors: Hong Yuen Wong, Grace M Wang, Sarah Croessmann, Daniel J Zabransky, David Chu, Joseph P Garay, Justin Cidado, Rory L Cochran, Julia A Beaver, Anita Aggarwal, Min-Ling Liu, Pedram Argani, Alan Meeker, Paula J Hurley, Josh Lauring, Ben Ho Park
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 42 Pg. 44927-40 (Dec 29 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 26702755 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Actins
• Tumor Suppressor Proteins
• thymosin beta(4)
• Thymosin

Topics

• Actins (genetics, metabolism)
• Breast Neoplasms, Male (genetics, metabolism, pathology)
• Cell Line
• Cell Proliferation
• Cell Shape
• Cell Transformation, Neoplastic (genetics, metabolism, pathology)
• Chromosomes, Human, Y
• Female
• Gene Deletion
• Gene Expression Regulation, Neoplastic
• Humans
• In Situ Hybridization, Fluorescence
• Male
• Mammary Glands, Human (metabolism, pathology)
• Phenotype
• Polymerase Chain Reaction
• Thymosin (genetics, metabolism)
• Time Factors
• Transfection
• Tumor Suppressor Proteins (genetics, metabolism)