Coppola, Luigi
(2017)
Targeting subtypes of breast cancer with Palbociclib, a cyclin-dependent Kinase inhibitor.
[Tesi di dottorato]
| Tipologia del documento: |
Tesi di dottorato
|
| Lingua: |
English |
| Titolo: |
Targeting subtypes of breast cancer with Palbociclib, a cyclin-dependent Kinase inhibitor |
| Autori: |
| Autore | Email |
|---|
| Coppola, Luigi | luigicoppola_@libero.it |
|
| Data: |
9 Aprile 2017 |
| Numero di pagine: |
48 |
| Istituzione: |
Università degli Studi di Napoli Federico II |
| Dipartimento: |
Medicina Molecolare e Biotecnologie Mediche |
| Dottorato: |
Medicina molecolare e biotecnologie mediche |
| Ciclo di dottorato: |
29 |
| Coordinatore del Corso di dottorato: |
| nome | email |
|---|
| Avvedimento, Vittorio Enrico | vittorioenrico.avvedimento@unina.it |
|
| Tutor: |
| nome | email |
|---|
| Veneziani, Bianca Maria | [non definito] |
|
| Data: |
9 Aprile 2017 |
| Numero di pagine: |
48 |
| Parole chiave: |
Breast cancer,Palbociclib |
| Settori scientifico-disciplinari del MIUR: |
Area 06 - Scienze mediche > MED/04 - Patologia generale |
[error in script]
[error in script]
| Depositato il: |
04 Mag 2017 12:31 |
| Ultima modifica: |
13 Mar 2018 11:23 |
| URI: |
http://www.fedoa.unina.it/id/eprint/11660 |
| DOI: |
10.6093/UNINA/FEDOA/11660 |
Abstract
Background: Breast cancer is the leading cause of cancer death in women. Despite major advances in breast cancer research, the recurrence of cancer represents a serious obstacle to successful treatment; deregulation in cell cycle proteins have been implicated in different cancers including breast. A pharmacological approach to inhibit cyclin - dependent kinases 4 and 6 (CDK 4/6) using Palbociclib, a highly selective small molecule inhibitor, was used to evaluate the effects of this inhibitor on cell proliferation of 4 different breast cancer cells subtypes (MCF-7, MDA-MB-231,BT474Z, MCF-7/her2 transfected).
Methods: ERα and Cyclin D1 expression has been evaluated on 34 breast cancer specimens; 4 human immortalized breast cancer cell lines (BT474Z, MCF-7, MCF7/her2 transfected, MDA-MB-231) and one cell line derived from breast cancer tissue patient (K90) have been treated with increasing concentrations of Palbociclib (cyclin D1-CDK4/6 inhibitor); cell proliferation was evaluate by MTT assay and cell count. Cell cycle analysis and protein expression have been performed by Facs and WB.
Results: ERα-positive MCF-7 cells are more sensitive to Palbociclib compared to the other breast cancer cell subtypes; Palbociclib displays a cytostatic effect by inhibiting cell viability and proliferation; the inhibitory effect of Palbociclib is based on breast cancer cells subtypes through modulation of expression of G0/G1 regulators (cyclin D1, p27, Rb and phospo-Rb).
Conclusion: This study suggests a potential role of CDK 4/6 inhibitor Palbociclib on different breast cancer subtypes and identifies Luminal A and Luminal B breast cancer as possible target of Palbociclib in clinical setting.
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