Differential Expression of TFF Genes and Proteins in Breast Tumors

Levak, Maja Tolušić; Mihalj, Martina; Koprivčić, Ivan; Lovrić, Ivana; Bijelić, Nikola; Baus-Lončar, Mirela; Belovari, Tatjana; Kralik, Kristina; Pauzar, Biljana

doi:10.20471/acc.2018.57.02.06

Cited by 4 publications

(3 citation statements)

References 41 publications

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“…To determine the localization and induction of the GFP fusion protein, the reporter cell lines were exposed to 1 nM E2 and imaged after 24 h. In line with previously published data for GREB1 ( Pellegrini et al , 2012 ) and TFF1 ( Levak et al , 2018 ), GREB1-GFP and TFF1-GFP are mainly expressed in the cytoplasm ( Figure 3B ). In contrast, PGR-GFP shows predominantly nuclear localization that is expected for the PGR transcription factor ( Lim et al , 1999 ) ( Figure 3B ).…”

Section: Resultssupporting

confidence: 73%

Physiologically Relevant Estrogen Receptor Alpha Pathway Reporters for Single-Cell Imaging-Based Carcinogenic Hazard Assessment of Estrogenic Compounds

Duijndam

Goudriaan

Hoorn

et al. 2021

Toxicological Sciences

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Estrogen receptor alpha (ERα) belongs to the nuclear hormone receptor family of ligand-inducible transcription factors and regulates gene networks in biological processes such as cell growth and proliferation. Disruption of these networks by chemical compounds with estrogenic activity, can result in adverse outcomes such as unscheduled cell proliferation, ultimately culminating in tumor formation. To distinguish disruptive activation from normal physiological responses, it is essential to quantify relationships between different key events leading to a particular adverse outcome. For this purpose, we established fluorescent protein MCF7 reporter cell lines for ERα-induced proliferation by bacterial artificial chromosome-based tagging of three ERα target genes: GREB1, PGR and TFF1. These target genes are inducible by the non-genotoxic carcinogen and ERα agonist 17β-estradiol in an ERα-dependent manner and are essential for ERα-dependent cell cycle progression and proliferation. The three GFP reporter cell lines were characterized in detail and showed different activation dynamics upon exposure to 17β-estradiol. In addition, they demonstrated specific activation in response to other established reference estrogenic compounds of different potencies, with similar sensitivities as validated OECD test methods. This study shows that these fluorescent reporter cell lines can be used to monitor the spatial and temporal dynamics of ERα pathway activation at the single cell level for more mechanistic insight, thereby allowing a detailed assessment of the potential carcinogenic activity of estrogenic compounds in humans.

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Section: Resultssupporting

confidence: 73%

Physiologically Relevant Estrogen Receptor Alpha Pathway Reporters for Single-Cell Imaging-Based Carcinogenic Hazard Assessment of Estrogenic Compounds

Duijndam

Goudriaan

Hoorn

et al. 2021

Toxicological Sciences

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“…2 A and 4 A ). These two small secretory proteins encoding by TFF1 and TFF2 are expressed mainly in the gastrointestinal tract and play an important role in mucosal restitution and repair processes ( Tolusic et al 2018 ). PTGES is a PSG in the bearded vulture, which encodes a glutathione-dependent prostaglandin E (PGE) synthase.…”

Section: Resultsmentioning

confidence: 99%

Vulture Genomes Reveal Molecular Adaptations Underlying Obligate Scavenging and Low Levels of Genetic Diversity

Zou

Tian

Zhang

et al. 2021

Molecular Biology and Evolution

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Obligate scavenging on dead and decaying animal matter is a rare dietary specialization that in extant vertebrates is restricted to vultures. These birds perform essential ecological services, yet many vulture species have undergone recent steep population declines and are now endangered. To test for molecular adaptations underlying obligate scavenging in vultures, and to assess whether genomic features might have contributed to their population declines, we generated high-quality genomes of the Himalayan and bearded vultures, representing both independent origins of scavenging within the Accipitridae, alongside a sister taxon, the upland buzzard. By comparing our data to published sequences from other birds, we show that the evolution of obligate scavenging in vultures has been accompanied by widespread positive selection acting on genes underlying gastric acid production, and immunity. Moreover, we find evidence of parallel molecular evolution, with amino acid replacements shared among divergent lineages of these scavengers. Our genome-wide screens also reveal that both the Himalayan and bearded vultures exhibit low levels of genetic diversity, equating to around a half of the mean genetic diversity of other bird genomes examined. However, demographic reconstructions indicate that population declines began at around the Last Glacial Maximum, predating the well-documented dramatic declines of the past three decades. Taken together, our genomic analyses imply that vultures harbour unique adaptations for processing carrion, but that modern populations are genetically depauperate and thus especially vulnerable to further genetic erosion through anthropogenic activities.

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“…Expression of TFF3 was more related to malignant tumors compared to the presence of TFF1. A correlation with TFF2 levels was not found ( 62 ). In comparison with other histotypes, the CA125 (MUC16) serum-marker is known to be a relatively weak predictor of relapse for MCs.…”

Section: Discussionmentioning

confidence: 99%

Trefoil factor family proteins as potential diagnostic markers for mucinous invasive ovarian carcinoma

Rönnerman

Pettersson²,

Nemes³

et al. 2023

Front. Oncol.

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IntroductionOvarian cancer (OC) is the leading cause of gynecological cancer-related death. Of the main OC histologic subtypes, invasive mucinous carcinomas (MC) account for only 3% of OC cases and are frequently associated with favorable prognosis. Nevertheless, MCs differ greatly from the other OC histotypes in clinical, pathological, and biological behavior. However, the origin and molecular pathogenesis of MC are not yet fully understood. Therefore, identification of novel diagnostic markers could potentially facilitate early diagnosis of OC, particularly the MC histotype, thereby leading to the development of histotype-specific treatment regimens and improved survival rates.MethodsIn the present study, Trefoil factor gene family members (TFF1, TFF2 and TFF3) were identified as MC histotype-specific biomarkers using RNA sequencing (RNA-seq) data for 95 stage I-II OCs. The diagnostic value of TFF1, TFF2 and TFF3 was then evaluated by immunohistochemistry on 206 stage I-II OCs stratified by histotype (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], clear cell carcinoma [CCC], and MC).ResultsWe showed significantly elevated intracytoplasmic protein expression levels for TFF1, TFF2 and TFF3 in MC samples, thereby revealing an association between expression of Trefoil factor gene family members and the MC histotype. Taken together, these findings suggest that the TFF proteins may play a pivotal role in tumor initiation and progression for the MC histotype.ConclusionTaken together, these findings suggest that the TFF proteins may play a pivotal role in tumor initiation and progression for the MC histotype. Moreover, these novel histotype-specific diagnostic biomarkers may not only improve patient stratification of early-stage ovarian carcinomas but may also be candidates for the development of molecular targeted therapies.

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Differential Expression of TFF Genes and Proteins in Breast Tumors

Cited by 4 publications

References 41 publications

Physiologically Relevant Estrogen Receptor Alpha Pathway Reporters for Single-Cell Imaging-Based Carcinogenic Hazard Assessment of Estrogenic Compounds

Physiologically Relevant Estrogen Receptor Alpha Pathway Reporters for Single-Cell Imaging-Based Carcinogenic Hazard Assessment of Estrogenic Compounds

Vulture Genomes Reveal Molecular Adaptations Underlying Obligate Scavenging and Low Levels of Genetic Diversity

Trefoil factor family proteins as potential diagnostic markers for mucinous invasive ovarian carcinoma

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