title: P16 and p53 play distinct roles in different subtypes of breast cancer.
abstract: Breast cancers are heterogeneous and complex diseases, and subtypes of breast cancers may involve unique molecular mechanisms. The p16(INK4a) and p53 pathways are two of the major pathways involved in control of the cell cycle. They also play key roles in tumorigenesis. However, whether the roles of these pathways differ in the subtypes of breast cancer is unclear. Therefore, p16 and p53 expression were investigated in different breast cancer subtypes to ascertain their contributions to these cancers. A total of 400 cases of non-invasive ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), including the major molecular subtypes luminal-A, luminal-B, Her-2, and triple-negative subtypes, and 50 cases of normal controls were compared. Luminal-A cancers expressed the lowest level of p16 among the subtypes in DCIS, and the level of p16 expression was up-regulated in the luminal-A of IDC (P<0.008). Triple-negative breast cancers were characterized by a correlation of p53 overexpression with a high level of p16 expression. Luminal lesion types with high p16 expression in DCIS were found to be more likely to develop into aggressive breast cancers, possibly promoted by p53 dysfunction. Taken together, the present study suggest that p16 expression in luminal-A breast cancers is associated with their progression from DCIS to IDC, and both p53 and p16 expressions are important for the development of triple-negative breast cancers in DCIS and IDC.
authors.affiliation: Department of Breast Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Shan
authors.forename: Xianyu
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Qin
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Ji
authors.initials: J
authors.lastname: Wang
authors.forename: Zhenbin
authors.initials: Z
authors.lastname: Zhong
authors.forename: Youxue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jingshu
authors.initials: J
authors.lastname: Geng
authors.forename: Da
authors.initials: D
authors.lastname: Pang
mesh_terms: D000293:Adolescent; D001943:Breast Neoplasms / Q000145:classification* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D012307:Risk Factors; D015398:Signal Transduction / Q000235:genetics; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D016159:Tumor Suppressor Protein p53