title: The regulation of SOX7 and its tumor suppressive role in breast cancer.
abstract: Both epigenetic silencing and genetic deletion of tumor suppressors contribute to the development and progression of breast cancer. SOX7 is a transcription factor important to development, and its down-regulation has been reported in tumor tissues and cell lines of prostate, colon, and lung cancers. However, the regulation of SOX7 expression and its functional role in breast cancer have not been reported. The current study demonstrates that SOX7 mRNA and protein expression are down-regulated in breast cancer tissues and cell lines compared with adjacent normal tissues and nontumorigenic cells, respectively. The SOX7 promoter is hypermethylated in breast cancer cell lines compared with nontumorigenic cells, and the inhibition of DNA methylation increases SOX7 mRNA levels. With shRNA-mediated SOX7 silencing, nontumorigenic immortal breast cells display increased proliferation, migration, and invasion and form structures that resemble that of breast cancer cells in a three-dimensional culture system. Conversely, ectopic SOX7 expression inhibits proliferation, migration, and invasion of breast cancer cells in vitro and tumor growth in vivo. Importantly, we discovered that SOX7 transcript levels positively correlated with clinical outcome of 674 breast cancer patients. Overall, our data suggest that SOX7 acts as a tumor suppressor in breast cancer. SOX7 expression is likely regulated by multiple mechanisms and potentially serves as a prognostic marker for breast cancer patients.
authors.affiliation: Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Stovall
authors.affiliation: Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
authors.forename: Meimei
authors.initials: M
authors.lastname: Wan
authors.affiliation: Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
authors.forename: Lance D
authors.initials: LD
authors.lastname: Miller
authors.affiliation: Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
authors.forename: Paul
authors.initials: P
authors.lastname: Cao
authors.affiliation: Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina; Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
authors.forename: Dejan
authors.initials: D
authors.lastname: Maglic
authors.affiliation: Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Life Science Division, Lawrence Berkeley National Laboratory, Berkeley, California.
authors.forename: Martha R
authors.initials: MR
authors.lastname: Stampfer
authors.affiliation: Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
authors.forename: Wennuan
authors.initials: W
authors.lastname: Liu
authors.affiliation: Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina; Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina. Electronic address: gsui@wakehealth.edu.
authors.forename: Guangchao
authors.initials: G
authors.lastname: Sui
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D011401:Promoter Regions, Genetic; D055760:SOXF Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C484456:SOX7 protein, human; D055760:SOXF Transcription Factors; D025521:Tumor Suppressor Proteins