title: Dual expression of alpha-tocopherol-associated protein and estrogen receptor in normal/benign human breast luminal cells and the downregulation of alpha-tocopherol-associated protein in estrogen-receptor-positive breast carcinomas.
abstract: The hormonal carcinogenesis of breast cancer involves hormone-driven cell proliferation and genetic alterations, including oncogene activation and suppressor gene inactivation. However, the predominant genes involved in these processes are currently unknown. Our previous studies identified a gene, namely alpha-tocopherol-associated protein, which is preferentially expressed in normal/benign breast and prostate tissue, but its expression is downregulated in breast and prostate carcinomas. To further examine its function in hormone-induced carcinogenesis, we examined if there is an association between alpha-tocopherol-associated protein and estrogen-receptor expression in normal/benign breast tissue and in human breast carcinomas. We found that alpha-tocopherol-associated protein is coexpressed with estrogen receptor in the luminal cells of normal/benign breast tissue in a scattered manner by immunohistochemical staining of consecutive tissue sections of 20 cases, whereas alpha-tocopherol-associated protein expression is downregulated in 46% (45 of 98) of estrogen-receptor/progesterone-receptor-positive, so-called luminal type A or B human breast carcinoma. This is similar to the association of alpha-tocopherol-associated protein and androgen receptor expression in normal/benign prostate and prostate carcinomas. In contrast,alpha-tocopherol-associated protein expression is mostly negative in basal, Her2 and triple-negative nonbasal subtypes of high-grade breast carcinomas. These findings are consistent with alpha-tocopherol-associated protein acting as an antiproliferative factor in estrogen-receptor-positive luminal cells in normal/benign breast tissue. alpha-Tocopherol-associated protein downregulation may have triggered hormonal carcinogenesis in at least some of the breast carcinomas, providing further, albeit indirect evidence to support a role for vitamin E in breast cancer prevention.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical School, Rochester, NY 14642, USA.
authors.forename: Sharlin
authors.initials: S
authors.lastname: Johnykutty
authors.forename: Ping
authors.initials: P
authors.lastname: Tang
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhao
authors.forename: David G
authors.initials: DG
authors.lastname: Hicks
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Yeh
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis*; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008074:Lipoproteins / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D015534:Trans-Activators / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D008074:Lipoproteins; D011960:Receptors, Estrogen; C432422:SEC14L2 protein, human; D015534:Trans-Activators