Abstract
Heterogeneous nuclear ribonucleoprotein K (hnRNPK) transcripts are abundant in estrogen receptor (ER)- or progesterone receptor (PR)-positive breast cancer. However, the biological functions of hnRNPK in the ER-mediated signaling pathway have remained largely unknown. Therefore, this study analyzes the functions of hnRNPK expression in the ER-mediated signaling pathway in breast cancer. We initially evaluated hnRNPK expression upon treatment with estradiol (E2) and ICI 182,780 in the ERα-positive breast carcinoma cell line MCF-7. The results revealed that E2 increased hnRNPK; however, hnRNPK expression was decreased with ICI 182,780 treatment, indicating estrogen dependency. We further evaluated the effects of hnRNPK knockdown in the ER-mediated signaling pathway in MCF-7 cells using small interfering RNAs. The results revealed that hnRNPK knockdown decreased ERα expression and ERα target gene pS2 by E2 treatment. As hnRNPK interacts with several other proteins, we explored the interaction between hnRNPK and ERα, which was demonstrated using immunoprecipitation and proximity ligation assay. Subsequently, we immunolocalized hnRNPK in patients with breast cancer, which revealed that hnRNPK immunoreactivity was significantly higher in ERα-positive carcinoma cells and significantly lower in Ki67-positive or proliferative carcinoma cells. These results indicated that hnRNPK directly interacted with ERα and was involved in the ER-mediated signaling pathway in breast carcinoma. Furthermore, hnRNPK expression could be an additional target of endocrine therapy in patients with ERα-positive breast cancer.
Highlights
Breast cancer is one of the most common cancers among women
HnRNPK is overexpressed in the nuclei and cytoplasm of several types of cancer cells, including head-andneck/oral squamous cell carcinomas (SCCA), its aberrant cytoplasmic localization is in the nuclei and cytoplasm of several types and of cancer cells, including head-and-neck/oral associated with poor prognosis, suggesting its involvement in cancer progression squamous cellacarcinomas (SCCA), and its aberrant cytoplasmic localization is associated a poor prognosis, suggesting involvement in cancer progression
We studied the expression of Heterogeneous nuclear ribonucleoprotein K (hnRNPK)
Summary
Breast cancer is one of the most common cancers among women. Estrogen, the primary female sex steroid hormone, and the estrogen receptor (ER) signaling pathway contribute to the progression of breast cancer [1]. HnRNPK is overexpressed in the nuclei and cytoplasm of several types of cancer cells, including head-andneck/oral squamous cell carcinomas (SCCA), its aberrant cytoplasmic localization is in the nuclei and cytoplasm of several types and of cancer cells, including head-and-neck/oral associated with poor prognosis, suggesting its involvement in cancer progression [5,6]. The possiTherefore, the possible interaction between hnRNPK and ER is reasonably postulated to ble interaction between and ER is reasonably postulated to be involved in the be involved in the ER-mediated signaling pathway of breast cancer. The biologER-mediated signaling pathway of breast cancer. We analyzed the function of as a binding protein in the binding protein in the ER-mediated signaling pathway in breast cancer.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
