Ovarian cáncer and Hippo pathway: characterization and estrogen modulation.

FRAUNHOFFER N.; MEILERMAN ABUELAFIA A.; STELLA I.; GALLIANO S; LOPEZ BERGAMI P.; VITULLO A

Mar del Plata

Congreso; Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2016

Sociedad Argentina de Investigación Clínica (SAIC)

Despite improvements in therapeutic strategies, prognosisfor patients 􀁙ith ovarian cancer 􀀊􀀱C􀀋 remains dismal. Hormonaltherapy could be an option. Tamoxifen and selective estrogenreceptor modulator, produce only a response of 􀀓􀀒􀀇 in 􀀱C. A􀁍ey player in hormonal therapy resistance may be the Hippopath􀁙ay 􀀊H􀀲􀀋 bypassing the classical estrogen cascade. 􀀻A􀀲 isa do􀁙nstream effector of H􀀲 binding to transcriptional co􀀏factorsTEA􀀦. 􀀻A􀀲 is phosphorylated and restricted to the cytoplasm by􀀯ST􀀓/􀀔􀀏 and LATS􀀓/􀀔􀀏 􀁍inases. To investigate H􀀲 involvementin 􀀱C, 􀁙e first analyzed the expression of 􀀻A􀀲, LATS􀀓 and􀀯ST􀀓/􀀔 by immunochemistry in 􀀓􀀖 􀀱C 􀀊􀀕 mucinous, 􀀖 serous,􀀖 endometrioid and 􀀕 clear cell􀀋. Samples 􀁙ere obtained fromHospital Eva 􀀲eron. 􀀹e found that ovarian cancer presenteddifferent pattern of 􀀻A􀀲 expression. Endometrioid and clear cellcarcinomas sho􀁙ed strong nuclear 􀀻A􀀲 expression in extracellularmatrix cells. 􀀱n the other hand, serous and mucinous carcinomaspresented nuclear 􀀻A􀀲 signal mainly in cancer cells. LATS􀀓 and􀀯ST􀀓/􀀔 sho􀁙ed lo􀁙 expression in all samples. 􀀫n order to analyzethe effect of 􀀓􀀙􀁅􀀏estradiol 􀀊E􀀔􀀋 on H􀀲 in 􀀱C, S􀀭􀀱􀀸􀀏􀀕 cells 􀁙eretreated 􀁙ith 􀀗􀀒 and 􀀓􀀒􀀒 n􀀯 of E􀀔. 􀀻A􀀲, p􀀏􀀻A􀀲 􀀊S􀀓􀀔􀀙􀀋, LATS􀀓and 􀀯ST􀀓/􀀔 expression 􀁙as analyzed by 􀁙estern blot at 􀀒, 􀀓 and􀀖h of treatment for each E􀀔 concentration. 􀀫n addition, cellularlocalization of 􀀻A􀀲 and TEA􀀦􀀖 􀁙as studied by 􀀫F. E􀀔 induceda reduction of p􀀏􀀻A􀀲 􀀊S􀀓􀀔􀀙􀀋 at 􀀓h in a dose of 􀀓􀀒􀀒 n􀀯. LATS􀀓and 􀀯ST􀀓/􀀔 levels 􀁙ere constant in all treatment conditions. Additionally,􀀻A􀀲 nuclear staining 􀁙as 􀀚􀀒􀀇 higher in 􀀓􀀒􀀒 n􀀯 at 􀀖 hthan control, 􀁙hile TEA􀀦􀀖 􀁙as 􀀖􀀒􀀇 higher. These results sho􀁙that 􀀻A􀀲 presents a differential pattern of expression dependingon 􀀱C type, but not LATS􀀓 and 􀀯ST􀀓/􀀔 􀁍inases 􀁙hich presentlo􀁙 levels in all 􀀱C types. Furthermore, our results suggest thatE􀀔 acts on H􀀲 promoting nuclear translocation of 􀀻A􀀲. Therefore,these results suggest that H􀀲 plays a role in ovarian tumorigenesisand hormonal therapy resistance.