지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2017.1
- 수록면
- 358 - 373 (16page)
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Purpose Prolactinoma (prolactin-secreting pituitary adenoma) is one of the most common estrogenrelated functional pituitary tumors. As an agonist of the dopamine D2 receptor, bromocriptine is used widely to inhibit prolactinoma progression. On the other hand, it is not always effective in clinical application. Although a dopamine D2 receptor deficiency contributes to the impaired efficiency of bromocriptine therapy to some extent, it is unknown whether there some other underlying mechanisms leading to bromocriptine resistance in prolactinoma treatment. That is the main point addressed in this project.
Materials and Methods Human prolactinoma samples were used to analyze the S-phase kinase associated protein 2 (SKP2) expression level. Nutlin-3/adriamycin/cisplatin-treated GH3 and MMQ cells were used to analyze apoptosis in SKP2 overexpression or knockdown cells. SKP2 expression and the interaction partners of SKP2 were also detected after a bromocriptine treatment in 293T. Apoptosis was analyzed in C25 and bromocriptine-treated GH3 cells.
Results Compared to normal pituitary samples, most prolactinoma samples exhibit higher levels of SKP2 expression, which could inhibit apoptosis in a p53-dependent manner. In addition, the bromocriptine treatment prolonged the half-life of SKP2 and resulted in SKP2 overexpression to a greater extent, which in turn compromised its pro-apoptotic effect. As a result, the bromocriptine treatment combined with C25 (a SKP2 inhibitor) led to the maximal apoptosis of human prolactinoma cells.
Conclusion These findings indicated that SKP2 inhibition sensitized the prolactinoma cells to bromocriptine and helped promote apoptosis. Moreover, a combined treatment of bromocriptine and C25 may contribute to the maximal apoptosis of human prolactinoma cells.
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참고문헌 (28)
참고문헌 신청
Amaral JD / 2010 / The role of p53in apoptosis / Discov Med 9 : 145 ~ 152
Booth AK / 2015 / Signaling pathways regulating pituitary lactotrope homeostasis and tumorigenesis / Adv Exp Med Biol 846 : 37 ~ 59
Cai L / 2016 / Dopamine agonist resistance-related endocan promotes angiogenesis and cells viability of prolactinomas / Endocrine 52 : 641 ~ 651
Caporali S / 2003 / Distinct signaling pathways mediate stimulation of cell cycle progression and prevention of apoptotic cell death by estrogen in rat pituitary tumor PR1 ce
Chan CH / 2013 / Pharmacological inactivation of Skp2 SCF ubiquitin ligase restricts cancer stem cell traits and cancer progression / Cell 154 : 556 ~ 568
Booth AK / 2015 / Signaling pathways regulating pituitary lactotrope homeostasis and tumorigenesis / Adv Exp Med Biol 846 : 37 ~ 59
Cai L / 2016 / Dopamine agonist resistance-related endocan promotes angiogenesis and cells viability of prolactinomas / Endocrine 52 : 641 ~ 651
Caporali S / 2003 / Distinct signaling pathways mediate stimulation of cell cycle progression and prevention of apoptotic cell death by estrogen in rat pituitary tumor PR1 ce
Chan CH / 2013 / Pharmacological inactivation of Skp2 SCF ubiquitin ligase restricts cancer stem cell traits and cancer progression / Cell 154 : 556 ~ 568
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