title: Hyaluronan synthase 2 overexpression is correlated with the tumorigenesis and metastasis of human breast cancer.
abstract: Extracellular matrix (ECM) is closely correlated with the malignant behavior of breast cancer cells. Hyaluronan (HA) is one of the main components of ECM, and actively regulates cell adhesion, migration and proliferation by interacting with specific cell surface receptors such as CD44 and RHAMM. HA synthase 2 (HAS2) catalyzes the synthesis of HA, but its role in breast tumorigenesis remains unclear. This study assessed the roles of HAS2 in malignant behavior of human breast cancer and sought to provide mechanistic insights into the biological and pivotal roles of HAS2. We observed HAS2 was overexpressed in breast cancer cell lines and invasive duct cancer tissues, compared with the nonmalignant breast cell lines and normal breast tissues. In addition, a high level of HAS2 expression was statistically correlated with lymph node metastasis. Functional assays showed that knockdown of HAS2 expression inhibited breast tumor cell proliferation in vivo and in vitro, through the induction of apoptosis or cell cycle arrest. Further studies showed that the HA were elevated in breast cancer, and HAS2 could upregulate HA expression. In conclusion, HAS2-HA system influences the biological characteristics of human breast cancer cells, and HAS2 may be a potential prognostic marker and therapeutic target in breast cancer.
authors.affiliation: Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University Chongqing 400016, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University Chongqing 400016, China.
authors.forename: Tingxiu
authors.initials: T
authors.lastname: Xiang
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University Chongqing 400016, China.
authors.forename: Hongzhong
authors.initials: H
authors.lastname: Li
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University Chongqing 400016, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University Chongqing 400016, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University Chongqing 400016, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University Chongqing 400016, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University Chongqing 400016, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University Chongqing 400016, China.
authors.forename: Jinxiang
authors.initials: J
authors.lastname: Tan
authors.affiliation: Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University Chongqing 400016, China.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Ren
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D063646:Carcinogenesis / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology / Q000473:pathology*; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D014453:Glucuronosyltransferase / Q000096:biosynthesis*; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000096:biosynthesis; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness / Q000473:pathology; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D059016:Tumor Microenvironment / Q000502:physiology; D015854:Up-Regulation
chemical_list: D034741:RNA, Small Interfering; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; C101754:HAS2 protein, human; D000076002:Hyaluronan Synthases
keywords: Breast cancer; RNA interference; hyaluronan; hyaluronan synthase 2; metastasis; tumorigenesis