Dataset Information

Sex differences in estrogen receptor subcellular location and activity in lung adenocarcinoma cells.

ABSTRACT: The role of estrogens in the increased risk of lung adenocarcinoma in women remains uncertain. We reported that lung adenocarcinoma cell lines from female, but not male, patients with non-small cell lung cancer respond proliferatively and transcriptionally to estradiol (E(2)), despite equal protein expression of estrogen receptors (ER) alpha and beta. To test the hypothesis that nuclear localization of ER alpha corresponds to genomic E(2) activity in lung adenocarcinoma cells from females, cell fractionation, immunoblot, and confocal immunohistochemical microscopy were performed. We report for the first time that E(2) increases phospho-serine-118-ER alpha (P-ser118-ER alpha) and cyclin D1 (CCND1) nuclear colocalization in H1793, but not A549 lung adenocarcinoma cells, derived from a female and male patient, respectively. ER beta was primarily in the cytoplasm and mitochondria, independent of E(2) treatment, and showed no difference between H1793 and A549 cells. E(2) induced higher transcription of endogenous ER alpha-regulated CCND1 in H1793 than in A549 cells. Likewise, higher rapid, non-genomic E(2)-induced extracellular signal-regulated kinase 1/2 activation was detected in H1793 compared with A549 cells, linking extracellular signal-regulated kinase activation to increased P-ser118-ER alpha. Furthermore, E(2) increased cyclin D1 and P-ser118-ER alpha nuclear localization in H1793, but not A549 cells. Together, our results indicate that nuclear localization of P-ser118-ER alpha provides one explanation for sex-dependent differences in E(2)-genomic responses in lung adenocarcinoma cell lines.

SUBMITTER: Ivanova MM

PROVIDER: S-EPMC2830404 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Sex differences in estrogen receptor subcellular location and activity in lung adenocarcinoma cells.

Ivanova Margarita M MM Mazhawidza Williard W Dougherty Susan M SM Klinge Carolyn M CM

American journal of respiratory cell and molecular biology 20090625 3

The role of estrogens in the increased risk of lung adenocarcinoma in women remains uncertain. We reported that lung adenocarcinoma cell lines from female, but not male, patients with non-small cell lung cancer respond proliferatively and transcriptionally to estradiol (E(2)), despite equal protein expression of estrogen receptors (ER) alpha and beta. To test the hypothesis that nuclear localization of ER alpha corresponds to genomic E(2) activity in lung adenocarcinoma cells from females, cell ...[more]

PMID: 19556604

Similar Datasets

Project description:BackgroundSex-related differences in cancer epidemiology, tumor biology, immune system activity, and pharmacogenomics have been suggested to be important considerations for precision cancer control. Here we elucidated systematically sex biases in genetic variants, gene expression profiles, and immunological landscapes of lung adenocarcinoma patients (LUADs) with different ancestry and smoking status.MethodsSomatic mutation and mRNA expression data of Asian and Non-Asian LUADs were obtained from public databases. Sex-biased genetic mutations, gene expression, biological pathways, and immune infiltration were identified in the context of smoking status and race.ResultsAmong nonsmokers, male-biased mutations were prevalent in Asian LUADs, while few sex-biased mutations were detected in Non-Asian LUADs. EGFR was the only mutation whose frequency was significantly higher in females than males in both Asian and Non-Asian nonsmokers. More genes exhibited sex-biased expression in Non-Asian LUADs compared to Asian LUADs. Moreover, genes distinctly expressed in females were mainly related to immune-related pathways, whereas those in males were more involved in activation of DNA repair, E2F_targets, and MYC_targets pathways. We also detected sex-specific immune infiltration in the context of genetic variation. In EGFR-mutant LUADs, males had a significantly increased infiltration of CD8 + T cells, whereas resting CD4 + memory T cells were more abundant in females. Additionally, in KRAS-mutant LUADs, CD8 + and CD4 + T cells were more abundant in females than males. In addition, we detected all female patients with high SCGB3A2 expression were exclusively sensitive to immunotherapy, while this phenomenon was not observed in male patients.ConclusionsOur findings provided evidence that sex-related molecular and cellular components are involved in shaping tumor distinct genetic and immune features, which might have important impact on personalized targeted and immune therapy.

Project description:TIPE3 (TNFAIP8L3), a transfer protein for lipid second messengers, is upregulated in human lung cancer tissues. The most popular lung cancer is non-small cell lung cancer (NSCLC) with high incidences and low survival rates, while the roles of TIPE3 in NSCLC remain largely unknown.TIPE3 expression was examined in tissue chips from patients with NSCLC using immunohistochemistry; the correlation of plasma membrane expression of TIPE3 with T stage of NSCLC was analyzed. After endogenous TIPE3 was silenced via siRNA, or TIPE3 with N or C-terminal flag was overexpressed via transient or stable transfection, human NSCLC cells were assayed for the proliferation and migration, respectively. NSCLC cells, in which TIPE3 with C-terminal flag was stably transfected, were inoculated into mice to establish xenograft tumors, the tumor growth and the expression of TIPE3 in tumor tissues were examined.TIPE3 was broadly expressed in lung tissues of patients with NSCLC. The plasma membrane expression of TIPE3 was positively correlated with the T stage of NSCLC. Knockdown of endogenous TIPE3, which was predominantly expressed in the plasma membrane, inhibited the proliferation and migration of NSCLC cells. While transient overexpression of TIPE3 with N-terminal flag, which was mostly trapped in the cytoplasm, inhibited the growth and migration of NSCLC cells accompanied by inactivation of AKT and ERK. In contrast, stable overexpression of TIPE3 with C-terminal flag, which could be localized in the plasma membrane, markedly promoted the growth and migration of NSCLC cells through activation of AKT and ERK. Notably, in xenograft tumor models established with NSCLC cells, stable overexpression of TIPE3 with C-terminal flag in NSCLC cells significantly promoted the tumor growth and enhanced the expression and plasma membrane localization of TIPE3 in tumor tissues.This study demonstrates that human TIPE3 promotes the proliferation and migration of NSCLC cells depending on its localization on plasma membrane, whereas cytoplasmic TIPE3 may exert a negative function. Thus, manipulating the subcellular location of TIPE3 can be a promising strategy for NSCLC therapy.

Dataset Information

Sex differences in estrogen receptor subcellular location and activity in lung adenocarcinoma cells.

Publications

Sex differences in estrogen receptor subcellular location and activity in lung adenocarcinoma cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets