Differentially androgen-modulated genes in ovarian epithelial cells from BRCA mutation carriers and control patients predict ovarian cancer survival and disease progression

Autor: Andreas Evangelou, Theodore J. Brown, A. Motamed-Khorasani, K J Murphy, Patricia Shaw, R K Parkes, Igor Jurisica, Barry P. Rosen, Xuejun Zhang, Michelle Letarte
Rok vydání: 2006
Předmět:
Adult
endocrine system
Cancer Research
Tumor suppressor gene
medicine.drug_class
Biology
medicine.disease_cause
Immunoenzyme Techniques
Genetics
medicine
Humans
RNA
Messenger
RNA
Neoplasm
Molecular Biology
Cells
Cultured
Aged
Oligonucleotide Array Sequence Analysis
Aged
80 and over
Ovarian Neoplasms
Leucine Zippers
Tissue microarray
BRCA1 Protein
Reverse Transcriptase Polymerase Chain Reaction
Gene Expression Profiling
Ovary
BRCA mutation
Cancer
Epithelial Cells
Middle Aged
Flow Cytometry
Androgen
medicine.disease
Carcinoma
Papillary
Cystadenocarcinoma
Serous
Gene Expression Regulation
Neoplastic
Survival Rate
Gene expression profiling
Basic-Leucine Zipper Transcription Factors
Tissue Array Analysis
Mutation
Acetylcholinesterase
Androgens
Disease Progression
Cancer research
Female
Ovarian cancer
Carcinogenesis
Carcinoma
Endometrioid
Zdroj: Oncogene. 26:198-214
ISSN: 1476-5594
0950-9232
Popis: Epidemiological studies have implicated androgens in the etiology and progression of epithelial ovarian cancer. We previously reported that some androgen responses were dysregulated in malignant ovarian epithelial cells relative to control, non-malignant ovarian surface epithelial (OSE) cells. Moreover, dysregulated androgen responses were observed in OSE cells derived from patients with germline BRCA-1 or -2 mutations (OSEb), which account for the majority of familial ovarian cancer predisposition, and such altered responses may be involved in ovarian carcinogenesis or progression. In the present study, gene expression profiling using cDNA microarrays identified 17 genes differentially expressed in response to continuous androgen exposure in OSEb cells and ovarian cancer cells as compared to OSE cells derived from control patients. A subset of these differentially affected genes was selected and verified by quantitative real-time reverse transcription-polymerase chain reaction. Six of the gene products mapped to the OPHID protein-protein interaction database, and five were networked within two interacting partners. Basic leucine zipper transcription factor 2 (BACH2) and acetylcholinesterase (ACHE), which were upregulated by androgen in OSEb cells relative to OSE cells, were further investigated using an ovarian cancer tissue microarray from a separate set of 149 clinical samples. Both cytoplasmic ACHE and BACH2 immunostaining were significantly increased in ovarian cancer relative to benign cases. High levels of cytoplasmic ACHE staining correlated with decreased survival, whereas nuclear BACH2 staining correlated with decreased time to disease recurrence. The finding that products of genes differentially responsive to androgen in OSEb cells may predict survival and disease progression supports a role for altered androgen effects in ovarian cancer. In addition to BACH2 and ACHE, this study highlights a set of potentially functionally related genes for further investigation in ovarian cancer.
Databáze: OpenAIRE
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