Changes related to phosphatidylinositol 3-kinase/Akt signaling in leiomyomas: possible involvement of glycogen synthase kinase 3a and cyclin D2 in the pathophysiology  

Oleh:

Karra, Laila ; Shushan, Asher ; Ben-Meir, Assaf

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Fertility and Sterility (keterangan: ada di ClinicalKey) vol. 93 no. 08 (Jun. 2010), page 2646-2651.
Topik: Uterine leiomyomas; signal transduction; PI3K/Akt; GSK3; cyclin D2; cell survival

Ketersediaan

Perpustakaan FK Nomor Panggil: F02.K.2010.03 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

Lihat Detail Induk

Isi artikel

Objective To identify changes in the expression and phosphorylation of phosphatidylinositol 3-kinase (PI3K)/Akt protein kinases controlling survival and/or apoptosis of in vitro cell cultures of uterine leiomyomas. Design Establishment of paired cell cultures of leiomyoma and myometrial specimens. Setting Hadassah gynecology research laboratory. Patient(s) Eleven white premenopausal women, 35 to 50 years of age, undergoing hysterectomy because of symptomatic uterine leiomyomas. Intervention(s) None. Main Outcome Measure(s) Immunochemical analysis of expression and phosphorylation of relevant PI3K/Akt and BCL2 proteins. Result(s) Analysis of total phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and of nonphosphorylated and phosphorylated (p) PDK1, Akt, glycogen synthase kinase 3 (GSK3), FKHR, tuberin (TSC2) and hamartin (TSC1) complex, and cyclin D2 proteins indicated that [1] the level of pGSK3a and cyclin D2 proteins was elevated significantly in the leiomyoma compared with the normal myometrium, [2] there was a significant interaction between PTEN- PDK1 and between pAkt-pGSK3ß in the leiomyoma compared with the myometrial cells, and [3] there was a significant interaction between pAkt-pGSK3a in the paired leiomyoma and myometrial cultures. Conclusion(s) Our study suggests that the downstream signaling components of the PI3K/Akt pathway, GSK3 (a regulator of apoptosis), and cyclin D2 (a promoter of G1/S progression), as well as the significant interaction between PTEN-PDK and between pAkt-pGSK3ß, are involved in the survival and proliferation of leiomyomas.

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