title: Testosterone regulates thyroid cancer progression by modifying tumor suppressor genes and tumor immunity.
abstract: Cancer gender disparity has been observed for a variety of human malignancies. Thyroid cancer is one such cancer with a higher incidence in women, but more aggressive disease in men. There is scant evidence on the role of sex hormones on cancer initiation/progression. Using a transgenic mouse model of follicular thyroid cancer (FTC), we found castration led to lower rates of cancer in females and less advanced cancer in males. Mechanistically, less advanced cancer in castrated males was due to increased expression of tumor suppressor (Glipr1, Sfrp1) and immune-regulatory genes and higher tumor infiltration with M1 macrophages and CD8 cells. Functional study showed that GLIPR1 reduced cell growth and increased chemokine secretion (Ccl5) that activates immune cells. Our data demonstrate that testosterone regulates thyroid cancer progression by reducing tumor suppressor gene expression and tumor immunity.
authors.affiliation: Endocrine Oncology Branch, Laboratory of Molecular Biology and Bioinformatics Core Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA and Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Zhang
authors.affiliation: Endocrine Oncology Branch, Laboratory of Molecular Biology and Bioinformatics Core Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA and Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Yin
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Endocrine Oncology Branch, Laboratory of Molecular Biology and Bioinformatics Core Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA and Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Naris
authors.initials: N
authors.lastname: Nilubol
authors.affiliation: Endocrine Oncology Branch, Laboratory of Molecular Biology and Bioinformatics Core Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA and Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: He
authors.affiliation: Endocrine Oncology Branch, Laboratory of Molecular Biology and Bioinformatics Core Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA and Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Swaroop
authors.initials: S
authors.lastname: Bommareddi
authors.affiliation: Laboratory of Molecular Biology and.
authors.forename: Xuguang
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Bioinformatics Core Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA and.
authors.forename: Li
authors.initials: L
authors.lastname: Jia
authors.affiliation: Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Laboratory of Molecular Biology and.
authors.forename: Jeong-Won
authors.initials: JW
authors.lastname: Park
authors.affiliation: Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.affiliation: Endocrine Oncology Branch, Laboratory of Molecular Biology and Bioinformatics Core Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA and Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Dhaval
authors.initials: D
authors.lastname: Patel
authors.affiliation: Laboratory of Molecular Biology and.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Willingham
authors.affiliation: Laboratory of Molecular Biology and.
authors.forename: Sheue-Yann
authors.initials: SY
authors.lastname: Cheng
authors.affiliation: Endocrine Oncology Branch, Laboratory of Molecular Biology and Bioinformatics Core Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA and Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA kebebewe@mail.nih.gov.
authors.forename: Electron
authors.initials: E
authors.lastname: Kebebew
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002369:Castration; D002460:Cell Line; D049109:Cell Proliferation; D018946:Chemokine CCL5 / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D057809:HEK293 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D017678:Sex Distribution; D013739:Testosterone / Q000378:metabolism*; D037042:Thyroid Hormone Receptors beta / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D018946:Chemokine CCL5; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D013739:Testosterone; D037042:Thyroid Hormone Receptors beta; C483024:CCL5 protein, human; C094538:GLIPR1 protein, human; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins