Ovarian cancer plasticity and epigenomics in the acquisition of a stem-like phenotype.

Aggressive epithelial ovarian cancer (EOC) is genetically and epigenetically distinct from normal ovarian surface epithelial cells (OSE) and early neoplasia. Co-expression of epithelial and mesenchymal markers in EOC suggests an involvement of epithelial-mesenchymal transition (EMT) in cancer initiation and progression. This phenomenon is often associated with acquisition of a stem cell-like phenotype and chemoresistance that correlate with the specific gene expression patterns accompanying transformation, revealing a plasticity of the ovarian cancer cell genome during disease progression.

Estrogen receptor-alpha hinge-region lysines 302 and 303 regulate receptor degradation by the proteasome.

Cellular levels of estrogen receptor-alpha (ERalpha) protein are regulated primarily by the ubiquitin-proteasome pathway. Dynamic interactions between ERalpha and the protein degradation machinery facilitate the down-regulation process by targeting receptor lysine residues for polyubiquitination. To date, the lysines that control receptor degradation have not been identified.

Transcriptional targeting in ovarian cancer cells using the human epididymis protein 4 promoter.

Objective: Limitations of current ovarian cancer gene therapies include lack of specificity and transduction of normal tissues. One strategy toward overcoming these limitations is to direct gene therapy specifically to ovarian cancer cells by using tissue- and tumor-specific promoters. The whey-acidic protein human epididymis protein 4 (HE4) is frequently overexpressed in ovarian cancer, suggesting that the HE4 promoter is highly transcriptionally active in the disease.