Fertility and sterility · 2009
Changes related to phosphatidylinositol 3-kinase/Akt signaling in leiomyomas: possible involvement of glycogen synthase kinase 3alpha and cyclin D2 in the pathophysiology.
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Karra Laila, Shushan Asher, Ben-Meir Assaf, Rojansky Nathan, Klein Benjamin Y, Shveiky David, Levitzki Rubina, Ben-Bassat Hanna
Аннотация
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 pGSK3alpha 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-pGSK3beta in the leiomyoma compared with the myometrial cells, and [3] there was a significant interaction between pAkt-pGSK3alpha 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-pGSK3beta, are involved in the survival and proliferation of 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 pGSK3alpha 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-pGSK3beta in the leiomyoma compared with the myometrial cells, and [3] there was a significant interaction between pAkt-pGSK3alpha 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-pGSK3beta, are involved in the survival and proliferation of leiomyomas.