title: Protein kinase C-α downregulates estrogen receptor-α by suppressing c-Jun phosphorylation in estrogen receptor-positive breast cancer cells.
abstract: Protein kinase C (PKC) activity is elevated in malignant compared with that in normal human breast tissue. In the present study, we investigated the regulatory mechanism and the co-relationship between PKC-α and estrogen receptor-α (ER-α) in ER-α-positive and tamoxifen-resistant (TAMR) breast cancer cells. Our results showed that the level of ER-α expression was significantly decreased in TAMR when compared with that in tamoxifen-sensitive (TAMS) breast cancer cells. However, PKC-α phosphorylation was increased in TAMR breast cancer cells when compared to that in TAMS breast cancer cells. Additionally, ER-α expression was significantly decreased due to the overexpression of constitutively active PKC-α (CA-PKC-α). Next, we investigated the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA), a reversible activator of PKC, on ER-α expression in ER-α-positive breast cancer cells. TPA decreased the levels of ER-α expression in a time- and dose-dependent manner. In contrast, the TPA-induced downregulation of ER-α was prevented by Go6983, a specific PKC inhibitor. Notably, we found that CA-PKC-α suppressed c-JUN phosphorylation, which is a major activating protein-1 factor, and TPA-induced downregulation of ER-α was prevented by SR11302, a specific activator protein-1 inhibitor. Taken together, we demonstrated that PKC-α activity suppressed the level of ER-α expression by inhibiting c-JUN phosphorylation in ER-α-positive breast cancer cells. Therefore, we suggest that PKC-α may be a potential therapeutic target for treating ER-positive and TAMR breast cancer.
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 135-710, Republic of Korea.
authors.forename: Sangmin
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 135-710, Republic of Korea.
authors.forename: Jeongmin
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 135-710, Republic of Korea.
authors.forename: Se Kyung
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 135-710, Republic of Korea.
authors.forename: Soo Youn
authors.initials: SY
authors.lastname: Bae
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 135-710, Republic of Korea.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 135-710, Republic of Korea.
authors.forename: Minkuk
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 135-710, Republic of Korea.
authors.forename: Won Ho
authors.initials: WH
authors.lastname: Kil
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 135-710, Republic of Korea.
authors.forename: Seok Won
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 135-710, Republic of Korea.
authors.forename: Jeong Eon
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 135-710, Republic of Korea.
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Nam
mesh_terms: D001943:Breast Neoplasms; D015536:Down-Regulation; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System; D061986:MCF-7 Cells; D010766:Phosphorylation; D051571:Protein Kinase C-alpha / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; C496628:PRKCA protein, human; D051571:Protein Kinase C-alpha