Consequences of the loss of p53, RB1, and PTEN: relationship to gefitinib resistance in endometrial cancer.

Consequences of the loss of p53, RB1, and PTEN: relationship to gefitinib resistance in endometrial cancer. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Consequences of the loss of p53, RB1, and PTEN: relationship to gefitinib resistance in endometrial cancer. Abstract Text:

Lina Albitar,Mark B Carter,Suzy Davies,Kimberly K Leslie,

OBJECTIVE: These studies demonstrate how loss of function mutations or downregulation of key tumor suppressors missing from type I and type II endometrial cancer cells contributes to carcinogenesis and to resistance to the EGFR inhibitor gefitinib (ZD1839). METHODS: Cell models devoid of tumor suppressors PTEN and RB1 or PTEN were studied. PTEN, RB1 and p53 expression was reinstated, and the effects on cell cycle, apoptosis, and cell cycle regulators were evaluated. RESULTS: In Ishikawa H cells that model type I endometrial cancer in the loss of PTEN and RB1, re-expressing PTEN and RB1 increased the apoptotic and G1 phases and decreased the S and G2-M phases, which further sensitize the cells to gefitinib. Expressing p53 in Hec50co that model type II tumors by loss of this tumor suppressor arrested cells at the G1-S checkpoint, and apoptosis was also induced. Yet this did not improve sensitivity to gefitinib. Modulation of the cell cycle regulators responsible for these changes is explored, and a potential new therapeutic target, MDM2, is identified. CONCLUSION: The downregulation of p53 expression in type II Hec50co cells is linked to gefitinib resistance. In addition, the overexpression of MDM2, the principal factor that inhibits p53 function also occurs in these resistant cells. MDM2 phosphorylation is only partially blocked by gefitinib, and high MDM2 expression may relate to drug resistance.

Consequences of the loss of p53, RB1, and PTEN: relationship to gefitinib resistance in endometrial cancer. Publishing Authors By Initials

L Albitar,MB Carter,S Davies,KK Leslie,

For similar proteins: dna-binding proteins: tumor suppressor protein p53 research abstracts see: proteins: dna-binding proteins: tumor suppressor protein p53 research

PUBMED ID PMID:

MEDLINE DATE:

Consequences of the loss of p53, RB1, and PTEN: relationship to gefitinib resistance in endometrial cancer. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Gynecologic oncology

VOLUME: 106

Page Numbers: 94-104

Journal Abbreviation: Gynecol. Oncol.

ISSN: 0090-8258

DAY: 8

MONTH: 05

YEAR: 2007

Consequences of the loss of p53, RB1, and PTEN: relationship to gefitinib resistance in endometrial cancer. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 365304

Consequences of the loss of p53, RB1, and PTEN: relationship to gefitinib resistance in endometrial cancer. Keywords Mesh Terms:

KEYWORDS: Tumor Suppressor Protein p53

MESH TERMS: genetics

Chemical & Substance for Abstract: Consequences of the loss of p53, RB1, and PTEN: relationship to gefitinib resistance in endometrial cancer. Information

Substance Name: PTEN Phosphohydrolase

Registry Number: EC 3.1.3.67

Grant and Affiliation Information for Consequences of the loss of p53, RB1, and PTEN: relationship to gefitinib resistance in endometrial cancer.

AFFILIATION: The Reproductive Molecular Biology Laboratory, Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, The University of New Mexico Health Science Center, Albuquerque, NM 87131, USA.

Country: United States

AGENCY: United States NCI

GRANT: R24 CA88339

ACRONYM: CA

MEDLINETA: Gynecol Oncol

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Consequences of the loss of p53, RB1, and PTEN: relationship to gefitinib resistance in endometrial cancer Related Publications

• 15-month-old infants detect violations in pretend scenarios.
• A common presentation with a rare cause.
• Age, sex and early environment contribute to individual differences in nicotine/acetaldehyde-induced behavioral and endocrine responses in rats.
• An evaluation of two indirect methods of estimating body weight in holstein calves and heifers.
• Anaesthesia for neurosurgery in the sitting position.
• Assessing penetration and aspiration: how do videofluoroscopy and fiberoptic endoscopic evaluation of swallowing compare?
• Challenges in improving fitness: results of a community-based, randomized, controlled lifestyle change intervention.
• Combining sequence and time series expression data to learn transcriptional modules.
• Consequences of the loss of p53, RB1, and PTEN: relationship to gefitinib resistance in endometrial cancer.
• Developmental regulation of nicotinic acetylcholine receptors within midbrain dopamine neurons.
• Gestational exposure to nicotine and monoamine oxidase inhibitors influences cocaine-induced locomotion in adolescent rats.
• Involvement of alpha1-adrenergic receptors in tranylcypromine enhancement of nicotine self-administration in rat.
• Living in a Glasshouse... embracing care issues beyond ICU.
• Low dose nicotine treatment during early adolescence increases subsequent cocaine reward.
• Models representing type I and type II human endometrial cancers: Ishikawa H and Hec50co cells.
• One world, one medicine.
• Ovarian function in Holstein cows immunized against pregnant mare serum gonadotrophin.
• Plasma concentrations of luteinizing hormone and progesterone during superovulation of dairy cows using follicle stimulating hormone or pregnant mare serum gonadotrophin.
• Predicting genetic regulatory response using classification.
• Relationship of estrogen and progesterone receptors to clinical outcome in metastatic endometrial carcinoma: a Gynecologic Oncology Group Study.
• Relative severity of aflatoxin contamination of cereal crops in West Africa.
• SVM-Fold: a tool for discriminative multi-class protein fold and superfamily recognition.
• Sample size requirements for bone density precision assessments and effect on patient categorization: a Monte Carlo simulation study.
• Stimulation of PI 3-kinase signaling via inhibition of the tumor suppressor phosphatase, PTEN.
• Synchronization of estrus and pregnancy risk in anestrous dairy cows after treatment with a progesterone-releasing intravaginal device.
• Targeted treatment using monoclonal antibodies and tyrosine-kinase inhibitors in pregnancy.
• The conceptual underpinnings of pretense: pretending is not 'behaving-as-if'.
• The role of advanced practice clinicians in the availability of abortion services in the United States.
• Timing of the onset and duration of ovulation in superovulated beef heifers.
• Type 1 diabetes and latent autoimmune diabetes in adults.