Stepwise estrogen suppression manipulating the estrostat.

P E Lønning

doi:10.1016/s0960-0760(01)00152-2

Home/Archive/PubMed

PubMed · 11850216

Stepwise estrogen suppression manipulating the estrostat.

P E Lønning

View original source ↗Export metadata ↓

Abstract

Estrogen suppression is an effective endocrine treatment option in pre- as well as postmenopausal breast cancer patients. The fact that it produces clinical benefits not only in these two groups of patients that differ significantly with respect to plasma estrogen levels but also among patients with very low plasma estrogen levels due to previous hypophysectomy, adrenalectomy or treatment with first/second generation aromatase inhibitors, suggests estrogen deprivation to work independent of pretreatment plasma estrogen levels. Interestingly, in vitro studies have revealed MCF-7 cells to respond to estrogen deprivation by sensitization, causing maximum estradiol stimulation at a concentration 10(-5) to 10(-4) the concentration needed in wild-type cells. While results from recent phase III studies comparing novel aromatase inhibitors and inactivators to conventional therapy have suggested that a more effective hormone ablation may be translated into an improved clinical efficacy, the biochemical rationale for lack of complete cross-resistance between aromatase inhibitors and inactivators or aromatase inhibitors and megestrol acetate remains to be explained. Interestingly, patients becoming resistant to estrogen deprivation may still respond to estrogens administered in pharmacological doses. Future studies are warranted to explore alterations in gene expression and signaling mechanisms in response to different therapies in tumor tissue in vivo.

Explore related subjects

Adaptation, Physiological Aromatase Inhibitors Breast Neoplasms Diethylstilbestrol Enzyme Inhibitors Estrogen Receptor Modulators Estrogens Female Humans Neoplasms, Hormone-Dependent Ovariectomy Research Design Journal Article Research Support, Non-U.S. Gov't Review

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

P E Lønning. 2001. Stepwise estrogen suppression manipulating the estrostat.. https://doi.org/10.1016/s0960-0760(01)00152-2

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2025

Genome sequencing and population genetics provide insights into local adaptation of Opisthopappus species on cliff environments of Taihang Mountains.

Local adaptation represents a pivotal theme in evolutionary biology. The Opisthopappus genus, comprising Opisthopappus longilobus and O. taihangensis, thrives on the cliffs of the Taihang Mountains. During their evolutionary history, two species are hypothesized to have locally adapted to their cliff habitats. In the present study, we employed a combined approach of whole-genome sequencing of O. taihangensis and population genomic analysis from both species to gain deeper insights into their patterns of local adaptation. Our results revealed that the expansive genome of O. taihangensis (3010.18 Mb), a consequence of a whole-genome duplication (WGD) event, coupled with a high proportion of repetitive sequences (82.70%), was postulated as one of its adaptive strategies. A clear differentiation between O. taihangensis and O. longilobus was observed, with the two species diverging approximately 17.57 million years ago (Mya), with O. longilobus serving as the ancestor. Since their divergence, limited gene flow was observed between the two species. Post-divergence, the effective population sizes of both species expanded, yet underwent a dramatic reduction at approximately 0.07 Mya. Furthermore, a total of 798 adaptive genes were identified, of which 207 overlapped with expanded genes, and eight genes were found to be under positive selection. These genes primarily regulated the growth and development of both species via pathways such as oxidation-reduction and ubiquitin-proteasome, enabling them to withstand climate changes. These findings provide profound insights into the local adaptation of Opisthopappus species to the cliff environments and offer valuable clues for further exploring the local adaptation among various cliff-dwelling organisms.

Adaptation, Physiological↗

PubMed2015

Variation in Drosophila melanogaster central metabolic genes appears driven by natural selection both within and between populations.

In this report, we examine the hypothesis that the drivers of latitudinal selection observed in the eastern US Drosophila melanogaster populations are reiterated within seasons in a temperate orchard population in Pennsylvania, USA. Specifically, we ask whether alleles that are apparently favoured in northern populations are also favoured early in the spring, and decrease in frequency from the spring to autumn with the population expansion. We use SNP data collected for 46 metabolic genes and 128 SNPs representing the central metabolic pathway and examine for the aggregate SNP allele frequencies whether the association of allele change with latitude and that with increasing days of spring-autumn season are reversed. Testing by random permutation, we observe a highly significant negative correlation between these associations that is consistent with this expectation. This correlation is stronger when we confine our analysis to only those alleles that show significant latitudinal changes. This pattern is not caused by association with chromosomal inversions. When data are resampled using SNPs for amino acid change the relationship is not significant but is supported when SNPs associated with cis-expression are only considered. Our results suggest that climate factors driving latitudinal molecular variation in a metabolic pathway are related to those operating on a seasonal level within populations.

Adaptation, Physiological↗

PubMed2007

A novel protein kinase family in Plasmodium falciparum is differentially transcribed and secreted to various cellular compartments of the host cell.

Processes at the surface of Plasmodium falciparum-infected erythrocytes such as antigenic variation and cytoadhesion may be modulated by active signalling between host and parasite. Potential candidates for this role include the putative kinases of the FIKK family. The novel Apicomplexa-specific FIKK gene has expanded in P. falciparum to 20 sequence-related members distributed between 11 chromosomes. Specific antibodies raised against different members indicated that most FIKK proteins locate to punctate foci in the erythrocyte cytoplasm that colocalized with Maurer's clefts proteins. One FIKK member dissociates at the trophozoite stage from the Maurer's clefts and relocates with the erythrocyte cytoskeleton. Another FIKK protein, despite having a PEXEL motif, remains located within the parasite. FIKK proteins possess the essential residues for phosphotransferase activity. We show that protein kinase activity was detected in immunoprecipitates obtained with two anti-FIKK antibodies. Quantitative PCR analysis revealed differential gene transcription of the FIKK paralogues in asexual blood stages parasites. We observed significant changes in the transcription pattern between parasites with different adhesion phenotypes. Our data suggest a role of FIKK proteins in the remodelling of the erythrocyte surface and reveal the existence of an adaptable parasite system able to sense intra- and possibly extracellular changes.

Adaptation, Physiological↗