The steroid receptor RNA activator protein is expressed in breast tumor tissues.
The steroid receptor RNA activator (SRA) was originally described as the first functional noncoding RNA able to specifically coactivate the activity of steroid receptors. We previously demonstrated the existence in breast cancer cell lines of new SRA isoforms that, as opposed to the first cloned SRA RNA, encode for a 236-amino acid protein, SRAP. To investigate the possible implications of the coding SRA RNA and SRAP expression on breast cancer progression, we examined by Western blot analysis 74 primary breast tumors of patients subsequently treated with tamoxifen. Patients whose primary tumors were positive for SRAP expression (n = 24) had a significantly (Kaplan-Meier survival curve p = 0.047) lower likelihood of dying from recurrent disease than SRAP-negative patients (n = 50). We generated 2 cell lines, SRAP-V5-High.A and SRAP-V5-High.B, by stably overexpressing SRAP in the estrogen receptor-positive MCF-7 breast cancer cell line. Transient transfection experiments, performed using a luciferase reporter gene under the control of an estrogen-responsive element, revealed decreased sensitivity to estradiol but no additional sensitivity to tamoxifen in SRAP-overexpressing cells. Overall, our data suggest that the presence of both coding SRA RNA and its corresponding SRAP modifies the activity of estrogen receptor in breast cancer cells and that SRAP could be a new clinical marker for breast cancer. Further studies are needed to define the respective mechanisms of action and the roles of SRA RNA and protein in breast tumorigenesis and tumor progression.
Chooniedass-Kothari
Shilpa
S
Department of Biochemistry and Medical Genetics, University of Manitoba, Faculty of Medicine, Winnipeg, Manitoba, Canada.
Hamedani
Mohammad Kariminia
MK
Troup
Sandy
S
Hubé
Florent
F
Leygue
Etienne
E
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000502:physiology; D016019:Survival Analysis; D013629:Tamoxifen / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D011960:Receptors, Estrogen; C405423:steroid receptor RNA activator; D013629:Tamoxifen