title: Estrogens Correlate with PELP1 Expression in ER Positive Breast Cancer.
abstract: The Proline-, glutamic acid- and leucine-rich protein 1 (PELP1) is an estrogen receptor (ER) coactivator and a proto-oncogene known to be deregulated in endocrine cancers. In breast cancer, PELP1 overexpression has been associated with endocrine therapy resistance. Although PELP1 is known to be regulated by estrogens in vitro, its association with estrogen levels within the tissue of breast cancer patients has not previously been assessed. Here, we determined PELP1 mRNA expression levels in paired samples of normal and malignant breast tissue obtained from 32 postmenopausal and 11 premenopausal women. In the total sample set, PELP1 levels were higher in tumors compared to normal breast tissue (P = 0.041). Among postmenopausal women, PELP1 tumor levels correlated positively with estrone (E1) and estradiol (E2) levels in both normal tissue (r = 0.543, P = 0.003 and r = 0.601, P = 0.001, respectively) and plasma (r = 0.392, P = 0.053 and r = 0.403, P = 0.046, respectively). Analyzing all ER+ tumors (n = 26), PELP1 correlated positively with E1 and E2 in tumor tissue (r = 0.562, P = 0.003 and r = 0.411, P = 0.037, respectively) and normal tissue (r = 0.461, P = 0.018 and r = 0.427, P = 0.030, respectively) in addition to plasma E1, E2 and estrone sulphate (E1S) concentrations (r = 0.576, P = 0.003, r = 0.456, P = 0.025 and r = 0.406, P = 0.049, respectively). Finally, PELP1 correlated positively with ER mRNA (ESR1) (r = 0.553, P = 0.026) in ER+ tumors, whereas a negative association between PELP1 and ESR1 (r = -0.733, P = 0.010) was observed in ER- breast tumors. Taken together, tumor PELP1 mRNA expression is associated with estrogen levels in breast cancer, suggesting a potentially important role of PELP1 in ER+ breast cancer growth in vivo.
authors.affiliation: Hormone Laboratory, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Marianne Hauglid
authors.initials: MH
authors.lastname: Flågeng
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Oncology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Stian
authors.initials: S
authors.lastname: Knappskog
authors.affiliation: Hormone Laboratory, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gjerde
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Oncology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Per Eystein
authors.initials: PE
authors.lastname: Lønning
authors.affiliation: Hormone Laboratory, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Mellgren
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D056970:Co-Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D004958:Estradiol / Q000032:analysis / Q000097:blood; D004967:Estrogens / Q000032:analysis* / Q000097:blood; D004970:Estrone / Q000031:analogs & derivatives / Q000032:analysis / Q000097:blood; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D017697:Premenopause; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D056970:Co-Repressor Proteins; D004967:Estrogens; C000715470:MAS1 protein, human; C438485:PELP1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D014157:Transcription Factors; D004970:Estrone; D004958:Estradiol; C017296:estrone sulfate