Amplification of CCND1 and PAK1 as predictors of recurrence and tamoxifen resistance in postmenopausal breast cancer

The 11q13 region is amplified in approximately 15% of all breast tumors. Situated in this region are the cyclin D1 gene ( CCND1 ) and the p-21-activated kinase 1 ( PAK1 ) gene. Both genes encode proteins shown to activate the estrogen receptor (ER), leading to transcription of CCND1 and other ER-res...

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Veröffentlicht in:	Oncogene 2007-10, Vol.26 (49), p.6997-7005
Hauptverfasser:	Bostner, J, Ahnström Waltersson, M, Fornander, T, Skoog, L, Nordenskjöld, B, Stål, O
Format:	Artikel
Sprache:	eng
Schlagworte:	Adult Aged Antineoplastic Agents, Hormonal - therapeutic use Antineoplastic Combined Chemotherapy Protocols - therapeutic use Apoptosis Biological and medical sciences Breast cancer Breast Neoplasms - diagnosis Breast Neoplasms - drug therapy Breast Neoplasms - genetics Cell Biology Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Chemotherapy, Adjuvant Cyclin D Cyclin D1 Cyclins - genetics Cyclins - metabolism Cyclophosphamide - therapeutic use Dosage and administration Drug resistance Drug Resistance, Neoplasm Drug therapy Estrogen receptors Female Fluorouracil - therapeutic use Fundamental and applied biological sciences. Psychology Gene Amplification Gene expression Genetic aspects Gynecology. Andrology. Obstetrics Health aspects Human Genetics Humans Internal Medicine Kinases Mammary gland diseases Medical sciences MEDICIN MEDICINE Medicine & Public Health Methotrexate - therapeutic use Middle Aged Molecular and cellular biology Neoplasm Recurrence, Local - diagnosis Neoplasm Recurrence, Local - genetics Oncology original-article p21-Activated Kinases - genetics p21-Activated Kinases - metabolism pak1 Patients Post-menopause Postmenopause Prognosis real-time PCR Reverse Transcriptase Polymerase Chain Reaction Risk factors RNA, Messenger - genetics RNA, Messenger - metabolism RNA, Neoplasm - genetics RNA, Neoplasm - metabolism Tamoxifen Tamoxifen - therapeutic use Transcription Tumors
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Zusammenfassung:	The 11q13 region is amplified in approximately 15% of all breast tumors. Situated in this region are the cyclin D1 gene ( CCND1 ) and the p-21-activated kinase 1 ( PAK1 ) gene. Both genes encode proteins shown to activate the estrogen receptor (ER), leading to transcription of CCND1 and other ER-responsive genes. Here, we investigate the prognostic and treatment predictive role of CCND1 and PAK1 gene amplification in postmenopausal breast cancer patients randomized to tamoxifen treatment or no adjuvant treatment. Amplification of CCND1 and PAK1 , assessed by real-time PCR, was observed in 12.5 and 9.3%, respectively. Amplification of PAK1 was seen in 37% of the CCND1 -amplified tumors, indicating coamplification ( P
ISSN:	0950-9232 1476-5594 1476-5594
DOI:	10.1038/sj.onc.1210506