PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Citation - WoS: 17Citation - Scopus: 19Pro-Metastatic Functions of Notch Signaling Is Mediated by Cyr61 in Breast Cells(Elsevier, 2020) Küçükköse, Cansu; Efe, Eda; Günyüz, Zehra Elif; Fıratlıgil, Burcu; Doğan, Hülya; Yalçın Özuysal, Özden; İlhan, MustafaMetastasis is the main cause of cancer related deaths, and unfolding the molecular mechanisms underlying metastatic progression is critical for the development of novel therapeutic approaches. Notch is one of the key signaling pathways involved in breast tumorigenesis and metastasis. Notch activation induces pro-metastatic processes such as migration, invasion and epithelial to mesenchymal transition (EMT). However, molecular mediators working downstream of Notch in these processes are not fully elucidated. CYR61 is a secreted protein implicated in metastasis, and its inhibition by a monoclonal antibody suppresses metastasis in xenograft breast tumors, indicating the clinical importance of CYR61 targeting. Here, we aimed to investigate whether CYR61 works downstream of Notch in inducing pro-metastatic phenotypes in breast cells. We showed that CYR61 expression is positively regulated by Notch activity in breast cells. Notch1-induced migration, invasion and anchorage independent growth of a normal breast cell line, MCF10A, were abrogated by CYR61 silencing. Furthermore, upregulation of core EMT markers upon Notch1-activation was impaired in the absence of CYR61. However, reduced migration and invasion of highly metastatic cell line, MDA MB 231, cells upon Notch inhibition was not dependent on CYR61 downregulation. In conclusion, we showed that in normal breast cell line MCF10A, CYR61 is a mediator of Notch1-induced pro-metastatic phenotypes partly via induction of EMT. Our results imply CYR61 as a prominent therapeutic candidate for a subpopulation of breast tumors with high Notch activity.Article Citation - WoS: 72Citation - Scopus: 75The Effects of Estrogen, Progesterone, and C-Erbb Receptor States on 18f-Fdg Uptake of Primary Breast Cancer Lesions(Society of Nuclear Medicine and Molecular Imaging, 2007) Mavi, Ayşe; Çermik, Tevfik F.; Urhan, Muammer; Püskülcü, Halis; Basu, Sandip; Yu, Jian Q.; Zhuang, Hongming; Czerniecki, Brian; Alavi, AbassThe purpose of this prospective study was to investigate whether correlations exist between 18F-FDG uptake of primary breast cancer lesions and predictive and prognostic factors such as estrogen receptor (ER), progesterone receptor (PR), and C-erbB-2 receptor (C-erbB-2R) states. Methods: Before undergoing partial or total mastectomy, 213 patients with newly diagnosed breast cancer underwent 18F-FDG PET (5.2 MBq/kg of body weight). The maximum standardized uptake value (SUV) of the primary lesion was measured in each patient. Standard immunohistochemistry was performed on a surgical specimen of the cancer lesion to characterize the receptor state of the tumor cells. Pearson χ2 tests were performed on the cross-tables of different receptor states to test any association that may exist among ER, PR, and C-erbB-2R. Maximum SUV measurements for different receptor states were compared using factorial ANOVA in a completely random design. Results: After exclusion of certain lesions, 118 lesions were analyzed for this study. The mean maximum SUVs of ER-positive and ER-negative lesions were 3.03 ± 0.26 and 5.64 ± 0.75, whereas those of PR were 3.24 ± 0.29 and 4.89 ± 0.67, respectively, and those of C-erbB-2R were 4.64 ± 0.70 and 3.70 ± 0.35, respectively, χ2 tests for ER and PR showed that if one is positive then the other tends to be positive as well (χ2 = 71.054, P < 0.01). For ER and C-erbB-2R states, if ER is positive, C-erbB-2R will more likely be negative (χ2 = 13.026, P < 0.01). No relationship was detected between PR and C-erbB-2R states (χ2 = 3.695, P > 0.05). ANOVAs showed that PR state alone (F = 0.095, P > 0.05) and C-erbB-2R state alone (F = 0.097, P > 0.05) had no effect on 18F-FDG uptake but ER state alone had an effect (F = 9.126, P < 0.01). ER and PR being together had no additional effect on 18F-FDG uptake. Our study also demonstrated that interactions exist between ER and C-erbB-2R state and between PR and C-erbB-2R state. Conclusion: SUV measurements may provide valuable information about the state of ER, PR, and C-erbB-2R and the associated glucose metabolism as measured by 18F-FDG uptake of the primary breast cancer lesions. Such an association may be of importance to treatment planning and outcome in these patients.