Proteomic analysis of a preneoplastic phenotype in ovarian surface epithelial cells derived from prophylactic oophorectomies.
OBJECTIVE
To study the pattern of protein expression associated with a predisposition to develop ovarian cancer.


METHODS
Prophylactic oophorectomy is used to prevent ovarian carcinoma in high-risk populations who have a strong family history of breast/ovarian cancer. In ovarian specimens of these women, the ovarian surface epithelium (OSE), which is tissue of origin of epithelial ovarian cancer, often shows altered morphology, growth patterns and differentiation features that are believed to be preneoplastic. This study has used a proteomic approach, based on two-dimensional gel electrophoresis and mass spectrometry, to compare the protein profiles of OSE from women with a history of familial ovarian cancer (FH-OSE), i.e., at least two first-degree relatives with such cancer and/or testing positive for BRCA1 mutations, to those without such history (NFH-OSE).


RESULTS
Of >1500 protein spots, there were 8 proteins whose levels were significantly altered in FH-OSE. Three were known ovarian tumor associated proteins, others were novel changes. A number of the alterations seen were accompanied with protein modifications and have not been previously reported. There was a predominance of sequences related to the stress response pathway. Differential expression of selected genes was confirmed by Western blotting and real-time reverse transcription polymerase chain reaction.


CONCLUSIONS
Our findings define the OSE phenotype of women at a high risk of developing ovarian cancer. Protein alterations seen in these tissues may represent an early, irreversible, non-mutational step in ovarian epithelial neoplastic progression and may be potential early and sensitive markers for the evaluation of cancer risk.
He
Qing-Yu
QY
Department of Chemistry, University of Hong Kong, Hong Kong; Open Laboratory of Chemical Biology of the Institute of Molecular Technology for Drug Discovery and Synthesis, University of Hong Kong, Hong Kong.
Zhou
Yuan
Y
Wong
Esther
E
Ehlen
Thomas G
TG
Auersperg
Nelly
N
Chiu
Jen-Fu
JF
Wong
Alice S T
AS
D000328:Adult; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D010052:Ovariectomy; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction
D009363:Neoplasm Proteins; D012333:RNA, Messenger