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1.
EMBO Mol Med ; 9(3): 304-318, 2017 03.
Article de Anglais | MEDLINE | ID: mdl-28179359

RÉSUMÉ

The angiogenic factor, VEGFA, is a therapeutic target in ovarian cancer (OVCA). VEGFA can also stimulate stem-like cells in certain cancers, but mechanisms thereof are poorly understood. Here, we show that VEGFA mediates stem cell actions in primary human OVCA culture and OVCA lines via VEGFR2-dependent Src activation to upregulate Bmi1, tumor spheres, and ALDH1 activity. The VEGFA-mediated increase in spheres was abrogated by Src inhibition or SRC knockdown. VEGFA stimulated sphere formation only in the ALDH1+ subpopulation and increased OVCA-initiating cells and tumor formation in vivo through Bmi1. In contrast to its action in hemopoietic malignancies, DNA methyl transferase 3A (DNMT3A) appears to play a pro-oncogenic role in ovarian cancer. VEGFA-driven Src increased DNMT3A leading to miR-128-2 methylation and upregulation of Bmi1 to increase stem-like cells. SRC knockdown was rescued by antagomir to miR-128. DNMT3A knockdown prevented VEGFA-driven miR-128-2 loss, and the increase in Bmi1 and tumor spheres. Analysis of over 1,300 primary human OVCAs revealed an aggressive subset in which high VEGFA is associated with miR-128-2 loss. Thus, VEGFA stimulates OVCA stem-like cells through Src-DNMT3A-driven miR-128-2 methylation and Bmi1 upregulation.


Sujet(s)
Épigenèse génétique , microARN/métabolisme , Cellules souches tumorales/physiologie , Tumeurs de l'ovaire/anatomopathologie , Complexe répresseur Polycomb-1/métabolisme , Facteur de croissance endothéliale vasculaire de type A/métabolisme , Aldéhyde déshydrogénase-1 , Lignée cellulaire tumorale , Prolifération cellulaire , Femelle , Humains , Isoenzymes/métabolisme , Retinal dehydrogenase/métabolisme , Régulation positive
2.
EMBO Mol Med ; 5(10): 1502-22, 2013 10.
Article de Anglais | MEDLINE | ID: mdl-23982961

RÉSUMÉ

Increasing evidence suggests that stem-like cells mediate cancer therapy resistance and metastasis. Breast tumour-initiating stem cells (T-ISC) are known to be enriched in CD44(+) CD24(neg/low) cells. Here, we identify two T-ISC subsets within this population in triple negative breast cancer (TNBC) lines and dissociated primary breast cancer cultures: CD44(+) CD24(low+) subpopulation generates CD44(+) CD24(neg) progeny with reduced sphere formation and tumourigenicity. CD44(+) CD24(low+) populations contain subsets of ALDH1(+) and ESA(+) cells, yield more frequent spheres and/or T-ISC in limiting dilution assays, preferentially express metastatic gene signatures and show greater motility, invasion and, in the MDA-MB-231 model, metastatic potential. CD44(+) CD24(low+) but not CD44(+) CD24(neg) express activated Notch1 intracellular domain (N1-ICD) and Notch target genes. We show N1-ICD transactivates SOX2 to increase sphere formation, ALDH1+ and CD44(+) CD24(low+) cells. Gamma secretase inhibitors (GSI) reduced sphere formation and xenograft growth from CD44(+) CD24(low+) cells, but CD44(+) CD24(neg) were resistant. While GSI hold promise for targeting T-ISC, stem cell heterogeneity as observed herein, could limit GSI efficacy. These data suggest a breast T-ISC hierarchy in which distinct pathways drive developmentally related subpopulations with different anti-cancer drug responsiveness.


Sujet(s)
Amyloid precursor protein secretases/antagonistes et inhibiteurs , Aldéhyde déshydrogénase-1 , Amyloid precursor protein secretases/métabolisme , Animaux , Antinéoplasiques/composition chimique , Antinéoplasiques/usage thérapeutique , Antinéoplasiques/toxicité , Antigènes CD24/métabolisme , Prolifération cellulaire/effets des médicaments et des substances chimiques , Antienzymes/composition chimique , Antienzymes/usage thérapeutique , Antienzymes/toxicité , Femelle , Humains , Antigènes CD44/métabolisme , Isoenzymes/métabolisme , Cellules MCF-7 , Souris , Souris de lignée BALB C , Souris nude , Cellules souches tumorales/cytologie , Cellules souches tumorales/effets des médicaments et des substances chimiques , Cellules souches tumorales/métabolisme , Récepteurs Notch/métabolisme , Retinal dehydrogenase/métabolisme , Facteurs de transcription SOX-B1/antagonistes et inhibiteurs , Facteurs de transcription SOX-B1/génétique , Facteurs de transcription SOX-B1/métabolisme , Tumeurs du sein triple-négatives/traitement médicamenteux , Tumeurs du sein triple-négatives/métabolisme , Tumeurs du sein triple-négatives/anatomopathologie , Cellules cancéreuses en culture
3.
Annu Rev Med ; 64: 45-57, 2013.
Article de Anglais | MEDLINE | ID: mdl-23121183

RÉSUMÉ

Obesity is a problem of epidemic proportions in many developed nations. Increased body mass index and obesity are associated with a significantly worse outcome for many cancers. Breast cancer risk in the postmenopausal setting and poor disease outcome for all patients is significantly augmented in overweight and obese individuals. The expansion of fat tissue involves a complex interaction of endocrine factors known as adipokines and cytokines. High cytokine levels in primary breast cancers and in the circulation of affected patients have been associated with poor outcome. This review summarizes the how cytokine production in obese adipose tissue creates a chronic inflammatory microenvironment that favors tumor cell motility, invasion, and epithelial-mesenchymal transition to enhance the metastatic potential of tumor cells. Many of the cytokines associated with a proinflammatory state are not only upregulated in obese adipose tissue but may also stimulate the self-renewal of cancer stem cells. Thus, enhanced cytokine production in obese adipose tissue may serve both as a chemoattractant for invading cancers and to augment their malignant potential. These new mechanistic insights suggest that the current obesity epidemic will presage a significant increase in cancer incidence, morbidity, and mortality in the next few decades.


Sujet(s)
Cytokines/métabolisme , Tumeurs , Obésité , Indice de masse corporelle , Évolution de la maladie , Santé mondiale , Humains , Incidence , Tumeurs/complications , Tumeurs/épidémiologie , Tumeurs/métabolisme , Obésité/complications , Obésité/épidémiologie , Obésité/métabolisme , Facteurs de risque
4.
Clin Cancer Res ; 18(21): 5911-23, 2012 Nov 01.
Article de Anglais | MEDLINE | ID: mdl-22896656

RÉSUMÉ

PURPOSE: More effective, less toxic treatments for recurrent ovarian cancer are needed. Although more than 60% of ovarian cancers express the estrogen receptor (ER), ER-targeted drugs have been disappointing due to drug resistance. In other estrogen-sensitive cancers, estrogen activates Src to phosphorylate p27 promoting its degradation and increasing cell-cycle progression. Because Src is activated in most ovarian cancers, we investigated whether combined Src and ER blockade by saracatinib and fulvestrant would circumvent antiestrogen resistance. EXPERIMENTAL DESIGN: ER and Src were assayed in 338 primary ovarian cancers. Dual ER and Src blockade effects on cell cycle, ER target gene expression, and survival were assayed in ERα+ ovarian cancer lines, a primary human ovarian cancer culture in vitro, and on xenograft growth. RESULTS: Most primary ovarian cancers express ER. Src activity was greater in ovarian cancer lines than normal epithelial lines. Estrogen activated Src, ER-Src binding, and ER translocation from cytoplasm to nucleus. Estrogen-mediated mitogenesis was via ERα, not ERß. While each alone had little effect, combined saracatinib and fulvestrant increased p27 and inhibited cyclin E-Cdk2 and cell-cycle progression. Saracatinib also impaired induction of ER-target genes c-Myc and FOSL1; this was greatest with dual therapy. Combined therapy induced autophagy and more effectively inhibited ovarian cancer xenograft growth than monotherapy. CONCLUSIONS: Saracatinib augments effects of fulvestrant by opposing estrogen-mediated Src activation and target gene expression, increasing cell-cycle arrest, and impairing survival, all of which would oppose antiestrogen resistance in these ER+ ovarian cancer models. These data support further preclinical and clinical evaluation of combined fulvestrant and saracatinib in ovarian cancer.


Sujet(s)
Antinéoplasiques/pharmacologie , Benzodioxoles/pharmacologie , Résistance aux médicaments antinéoplasiques , Oestradiol/analogues et dérivés , Tumeurs de l'ovaire/métabolisme , Quinazolines/pharmacologie , Récepteurs des oestrogènes/métabolisme , src-Family kinases/antagonistes et inhibiteurs , Animaux , Antinéoplasiques/administration et posologie , Apoptose/effets des médicaments et des substances chimiques , Benzodioxoles/administration et posologie , Lignée cellulaire tumorale , Noyau de la cellule/métabolisme , Prolifération cellulaire/effets des médicaments et des substances chimiques , Modèles animaux de maladie humaine , Activation enzymatique/effets des médicaments et des substances chimiques , Oestradiol/administration et posologie , Oestradiol/pharmacologie , Oestrogènes/pharmacologie , Femelle , Fulvestrant , Régulation de l'expression des gènes tumoraux/effets des médicaments et des substances chimiques , Techniques de knock-down de gènes , Humains , Souris , Tumeurs de l'ovaire/traitement médicamenteux , Tumeurs de l'ovaire/génétique , Liaison aux protéines , Transport des protéines , Quinazolines/administration et posologie , Récepteurs des oestrogènes/antagonistes et inhibiteurs , Tests d'activité antitumorale sur modèle de xénogreffe , src-Family kinases/génétique
5.
J Clin Invest ; 121(4): 1349-60, 2011 Apr.
Article de Anglais | MEDLINE | ID: mdl-21364280

RÉSUMÉ

Fine tuning of the protein folding environment in subcellular organelles, such as mitochondria, is important for adaptive homeostasis and may participate in human diseases, but the regulators of this process are still largely elusive. Here, we have shown that selective targeting of heat shock protein-90 (Hsp90) chaperones in mitochondria of human tumor cells triggered compensatory autophagy and an organelle unfolded protein response (UPR) centered on upregulation of CCAAT enhancer binding protein (C/EBP) transcription factors. In turn, this transcriptional UPR repressed NF-κB-dependent gene expression, enhanced tumor cell apoptosis initiated by death receptor ligation, and inhibited intracranial glioblastoma growth in mice without detectable toxicity. These data reveal what we believe to be a novel role of Hsp90 chaperones in the regulation of the protein-folding environment in mitochondria of tumor cells. Disabling this general adaptive pathway could potentially be used in treatment of genetically heterogeneous human tumors.


Sujet(s)
Mitochondries/métabolisme , Tumeurs/métabolisme , Tumeurs/thérapie , Réponse aux protéines mal repliées , Animaux , Apoptose , Tumeurs du cerveau/traitement médicamenteux , Tumeurs du cerveau/génétique , Tumeurs du cerveau/métabolisme , Tumeurs du cerveau/anatomopathologie , Protéines liant les séquences stimulatrices de type CCAAT/métabolisme , Lignée cellulaire tumorale , Expression des gènes , Techniques de knock-down de gènes , Glioblastome/traitement médicamenteux , Glioblastome/génétique , Glioblastome/métabolisme , Glioblastome/anatomopathologie , Guanidines/pharmacologie , Protéines du choc thermique HSP90/métabolisme , Humains , Lactames macrocycliques/pharmacologie , Souris , Souris nude , Mitochondries/effets des médicaments et des substances chimiques , Facteur de transcription NF-kappa B/métabolisme , Tumeurs/génétique , Petit ARN interférent/génétique , Transduction du signal , Stress physiologique , Ligand TRAIL/pharmacologie
6.
Cancer Res ; 70(17): 6870-9, 2010 Sep 01.
Article de Anglais | MEDLINE | ID: mdl-20736377

RÉSUMÉ

Malignant gliomas are treated with a combination of surgery, radiation, and temozolomide (TMZ), but these therapies ultimately fail due to tumor recurrence. In glioma cultures, TMZ treatment significantly decreases neurosphere formation; however, a small percentage of cells survive and repopulate the culture. A promising target for glioma therapy is the Notch signaling pathway. Notch activity is upregulated in many gliomas and can be suppressed using gamma-secretase inhibitors (GSI). Using a neurosphere recovery assay and xenograft experiments, we analyzed if the addition of GSIs with TMZ treatment could inhibit repopulation and tumor recurrence. We show that TMZ + GSI treatment decreased neurosphere formation and inhibited neurosphere recovery. This enhancement of TMZ treatment occurred through inhibition of the Notch pathway and depended on the sequence of drug administration. In addition, ex vivo TMZ + GSI treatment of glioma xenografts in immunocompromised mice extended tumor latency and survival, and in vivo TMZ + GSI treatment blocked tumor progression in 50% of mice with preexisting tumors. These data show the importance of the Notch pathway in chemoprotection and repopulation of TMZ-treated gliomas. The addition of GSIs to current treatments is a promising approach to decrease brain tumor recurrence.


Sujet(s)
Amyloid precursor protein secretases/antagonistes et inhibiteurs , Antinéoplasiques alcoylants/pharmacologie , Protocoles de polychimiothérapie antinéoplasique/pharmacologie , Tumeurs du cerveau/traitement médicamenteux , Dacarbazine/analogues et dérivés , Glioblastome/traitement médicamenteux , Animaux , Tumeurs du cerveau/enzymologie , Tumeurs du cerveau/anatomopathologie , Lignée cellulaire tumorale , Dacarbazine/administration et posologie , Dacarbazine/pharmacologie , Dipeptides/administration et posologie , Dipeptides/pharmacologie , Glioblastome/enzymologie , Glioblastome/anatomopathologie , Humains , Souris , Récidive tumorale locale/traitement médicamenteux , Récidive tumorale locale/enzymologie , Récidive tumorale locale/anatomopathologie , ARN messager/biosynthèse , ARN messager/génétique , Récepteurs Notch/biosynthèse , Récepteurs Notch/génétique , Récepteurs Notch/métabolisme , Transduction du signal/effets des médicaments et des substances chimiques , Sphéroïdes de cellules , Témozolomide , Cellules cancéreuses en culture , Tests d'activité antitumorale sur modèle de xénogreffe
7.
Neurosci Lett ; 478(3): 165-70, 2010 Jul 12.
Article de Anglais | MEDLINE | ID: mdl-20470863

RÉSUMÉ

Despite conventional treatment strategies glioblastoma, the most common malignant primary brain tumor, has a bad prognosis with median survival times of 12-15 months. In this study, the efficacy of sorafenib (Nexavar, BAY43-9006), a multikinase inhibitor, on glioblastoma cells was evaluated both in vitro and in vivo. Treatment of established or patient-derived glioblastoma cells with low concentrations of sorafenib caused a dramatic dose dependent inhibition of proliferation (IC(50), 1.5 microM) and induction of apoptosis and autophagy. Sorafenib inhibited phosphorylation of signal transducer and activator of transcription 3 (Stat3) and expression of cyclins, D and E. In contrast, AKT was not modulated by sorafenib. Most important, systemic delivery of sorafenib was well tolerated, and significantly suppressed intracranial glioma growth via inhibition of cell proliferation, induction of apoptosis and autophagy, and reduction of angiogenesis. Furthermore, intracranial growth inhibition by sorafenib was accompanied by a significant reduction in ph-Stat3 (Tyr 705) levels. In summary, sorafenib has potent anti-glioma activity in vitro and in vivo.


Sujet(s)
Antinéoplasiques/pharmacologie , Benzènesulfonates/pharmacologie , Tumeurs du cerveau/traitement médicamenteux , Glioblastome/traitement médicamenteux , Pyridines/pharmacologie , Animaux , Antinéoplasiques/administration et posologie , Antinéoplasiques/effets indésirables , Apoptose/effets des médicaments et des substances chimiques , Apoptose/physiologie , Autophagie/effets des médicaments et des substances chimiques , Autophagie/physiologie , Benzènesulfonates/administration et posologie , Benzènesulfonates/effets indésirables , Tumeurs du cerveau/métabolisme , Tumeurs du cerveau/anatomopathologie , Lignée cellulaire tumorale , Prolifération cellulaire/effets des médicaments et des substances chimiques , Modèles animaux de maladie humaine , Relation dose-effet des médicaments , Femelle , Glioblastome/métabolisme , Glioblastome/anatomopathologie , Gliome/traitement médicamenteux , Gliome/métabolisme , Gliome/anatomopathologie , Souris , Souris nude , Transplantation tumorale , Néovascularisation pathologique/traitement médicamenteux , Néovascularisation pathologique/métabolisme , Néovascularisation pathologique/anatomopathologie , Nicotinamide/analogues et dérivés , Phénylurées , Inhibiteurs de protéines kinases/pharmacologie , Pyridines/administration et posologie , Pyridines/effets indésirables , Répartition aléatoire , Sorafénib , Résultat thérapeutique
8.
Cancer Lett ; 296(2): 168-77, 2010 Oct 28.
Article de Anglais | MEDLINE | ID: mdl-20435409

RÉSUMÉ

Glioblastoma patients have a poor prognosis, even after surgery, radiotherapy, and chemotherapy with temozolomide or 1,3-bis(2-chloroethy)-1-nitrosourea. We developed an in vitro recovery model using neurosphere cultures to analyze the efficacy of chemotherapy treatments, and tested whether glioblastoma neurosphere-initiating cells are resistant. Concentrations of chemotherapy drugs that inhibit neurosphere formation are similar to clinically relevant doses. Some lines underwent a transient cell cycle arrest and a robust recovery of neurosphere formation. These results indicate that glioblastoma neurospheres can regrow after treatment with chemotherapy drugs. This neurosphere recovery assay will facilitate studies of chemo-resistant subpopulations and methods to enhance glioblastoma therapy.


Sujet(s)
Dacarbazine/analogues et dérivés , Glioblastome/traitement médicamenteux , Animaux , Antinéoplasiques/usage thérapeutique , Antinéoplasiques alcoylants/usage thérapeutique , Carmustine/usage thérapeutique , Adhérence cellulaire , Techniques de culture cellulaire , Mort cellulaire , Division cellulaire , Lignée cellulaire tumorale , Amorces ADN , ADN complémentaire/génétique , Dacarbazine/usage thérapeutique , Exons , Glioblastome/anatomopathologie , Glioblastome/physiopathologie , Glioblastome/radiothérapie , Glioblastome/chirurgie , Humains , Souris , Souris nude , Récidive tumorale locale , Pronostic , Témozolomide , Transplantation hétérologue , Résultat thérapeutique
9.
Mol Cancer Ther ; 9(6): 1638-46, 2010 Jun.
Article de Anglais | MEDLINE | ID: mdl-20501802

RÉSUMÉ

Drug discovery for complex and heterogeneous tumors now aims at dismantling global networks of disease maintenance, but the subcellular requirements of this approach are not understood. Here, we simultaneously targeted the multiple subcellular compartments of the molecular chaperone heat shock protein-90 (Hsp90) in a model of glioblastoma, a highly lethal human malignancy in urgent need of fresh therapeutic strategies. Treatment of cultured or patient-derived glioblastoma cells with Shepherdin, a dual peptidomimetic inhibitor of mitochondrial and cytosolic Hsp90, caused irreversible collapse of mitochondria, degradation of Hsp90 client proteins in the cytosol, and tumor cell killing by apoptosis and autophagy. Stereotactic or systemic delivery of Shepherdin was well tolerated and suppressed intracranial glioma growth via inhibition of cell proliferation, induction of apoptosis, and reduction of angiogenesis in vivo. These data show that disabling Hsp90 cancer networks in their multiple subcellular compartments improves strategies for drug discovery and may provide novel molecular therapy for highly recalcitrant human tumors.


Sujet(s)
Glioblastome/métabolisme , Glioblastome/thérapie , Protéines du choc thermique HSP90/antagonistes et inhibiteurs , Adulte , Sujet âgé , Animaux , Antinéoplasiques/pharmacologie , Autophagie/effets des médicaments et des substances chimiques , Lignée cellulaire tumorale , Prolifération cellulaire/effets des médicaments et des substances chimiques , Peptidyl-prolyl isomerase F , Cyclophilines/métabolisme , Femelle , Glioblastome/anatomopathologie , Protéines du choc thermique HSP90/métabolisme , Humains , Mâle , Souris , Adulte d'âge moyen , Mitochondries/effets des médicaments et des substances chimiques , Mitochondries/anatomopathologie , Protéines mitochondriales/métabolisme , Fragments peptidiques/pharmacologie , Fractions subcellulaires/effets des médicaments et des substances chimiques , Fractions subcellulaires/métabolisme , Tests d'activité antitumorale sur modèle de xénogreffe
10.
J Cell Biochem ; 108(5): 1031-8, 2009 Dec 01.
Article de Anglais | MEDLINE | ID: mdl-19760641

RÉSUMÉ

A cancer stem cell (CSC) is defined as an undifferentiated cell with the ability to self-renew, differentiate to multiple lineages and initiate tumors that mimic the parent tumor. In this review, we focus on glioblastomas, describing recent progress and problems in characterizing these cells. There have been advances in CSC culture, but tumor cell heterogeneity has made purification of CSCs difficult. Indeed, it may be that CSCs significantly vary from tumor to tumor. We also discuss the proposal that CSCs are resistant to radiotherapy and chemotherapy and play a major role in repopulating tumors following treatment. To overcome their resistance to conventional therapies, we may be able to use our extensive knowledge of the signaling pathways essential for stem cells during development. These pathways have potential as targets for new glioblastoma therapies. Hence, although there is an ongoing debate on the nature of CSCs, the theory continues to suggest new ideas for both the lab and the clinic.


Sujet(s)
Marqueurs biologiques tumoraux , Cellules souches tumorales , Tumeurs du cerveau/traitement médicamenteux , Tumeurs du cerveau/anatomopathologie , Tumeurs du cerveau/radiothérapie , Techniques de culture cellulaire , Différenciation cellulaire , Lignage cellulaire , Prolifération cellulaire , Transformation cellulaire néoplasique , Milieux de culture , Résistance aux médicaments antinéoplasiques/physiologie , Glioblastome/traitement médicamenteux , Glioblastome/anatomopathologie , Glioblastome/radiothérapie , Humains , Modèles biologiques , Cellules souches tumorales/anatomopathologie , Cellules souches tumorales/physiologie , Transduction du signal/physiologie
11.
Physiol Behav ; 93(3): 560-9, 2008 Feb 27.
Article de Anglais | MEDLINE | ID: mdl-18035382

RÉSUMÉ

Dietary restriction (DR) has been shown to increase life span and reduce disease incidence across a variety of species. Recent research suggests that chronic adult DR may also alter age-related cognitive decline. The purpose of this study was twofold: (1) to examine the potential deficits in spatial learning ability in the aged F344 x BN hybrid F1 rat with specific attention to the contributory effects of motoric impairments and (2) to determine the influence of chronic adult DR on any such impairments. The Morris water maze (MWM) task was employed with a 1.8 m diameter tank, 10 cm2 escape platform, 28 degrees C water, and an automated collapsing central starting platform. Spatial learning impairments in the aged rats were evident on all dependent measures during training and the probe test. Motoric function, as reflected in measures of strength and locomotion demonstrated profound age-related performance impairments that were attenuated by chronic adult DR. The present data also replicate previous reports, indicating that DR attenuates the age-related impairments of performance in the MWM as indexed by the latency measure in acquisition, but critically was dissociated from any DR effect on measures of preference and, more critically, accuracy in the probe test. Collectively, the most parsimonious interpretation of DR effects on MWM performance would appear to be the preservation of motoric, and not cognitive, function.


Sujet(s)
Vieillissement , Comportement animal/physiologie , Régime alimentaire , Apprentissage du labyrinthe/physiologie , Perception de l'espace/physiologie , Analyse de variance , Animaux , Apprentissage par évitement , Poids , Croisements génétiques , Activité motrice/physiologie , Performance psychomotrice , Rats , Rats de lignée BN , Rats de lignée F344 , Temps de réaction , Spécificité d'espèce , Natation , Facteurs temps
12.
Genetics ; 173(3): 1599-611, 2006 Jul.
Article de Anglais | MEDLINE | ID: mdl-16648586

RÉSUMÉ

On both recent and ancient time scales, polyploidy (genome doubling) has been a significant evolutionary force in plants. Here, we examined multiple individuals from reciprocally formed populations of Tragopogon miscellus, an allotetraploid that formed repeatedly within the last 80 years from the diploids T. dubius and T. pratensis. Using cDNA-AFLPs followed by genomic and cDNA cleaved amplified polymorphic sequence (CAPS) analyses, we found differences in the evolution and expression of homeologous loci in T. miscellus. Fragment variation within T. miscellus, possibly attributable to reciprocal formation, comprised 0.6% of the cDNA-AFLP bands. Genomic and cDNA CAPS analyses of 10 candidate genes revealed that only one "transcript-derived fragment" (TDF44) showed differential expression of parental homeologs in T. miscellus; the T. pratensis homeolog was preferentially expressed by most polyploids in both populations. Most of the cDNA-AFLP polymorphisms apparently resulted from loss of parental fragments in the polyploids. Importantly, changes at the genomic level have occurred stochastically among individuals within the independently formed populations. Synthetic F(1) hybrids between putative diploid progenitors are additive of their parental genomes, suggesting that polyploidization rather than hybridization induces genomic changes in Tragopogon.


Sujet(s)
Évolution moléculaire , Régulation de l'expression des gènes végétaux , Polyploïdie , Tragopogon/génétique , ADN complémentaire/métabolisme , Diploïdie , Génétique des populations , Génome végétal , Hybridation génétique , Données de séquences moléculaires , Polymorphisme de conformation simple brin , Graines/cytologie , Graines/croissance et développement , Graines/métabolisme
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