Thesis (Ph.D.) - Cairo University - National Cancer Institute - Department of Oncologic (Pathology)

Ovarian cancer is the 7th commonest cancer in women and is considered the most lethal gynecologic malignancy. Chemo-resistance is the major obstacle for the treatment of ovarian cancer. With the adopted treatment strategies, up to 90% of patients suffer relapse. The role of Prolactin (PRL)/ Prolactin Receptor (PRL-R) signaling has been suggested in many types of cancer and some studies suggested that PRL opposes cytotoxicity of many anticancer drugs. Material and Methods We investigated the profile and significance of expression of PRL-R and all its ligands in 503 ovarian surface epithelial tumours and cell lines by immunohistochemistry (IHC) and Western blotting and we studied the effect of PRL-R knockdown and antagonism on the viability, apoptosis and response to chemotherapy in ovarian HGSC cell lines. Results PRL-R is expressed in all cases of ovarian tumours by and both long and short PRL-R isoforms are expressed in HGSC cell lines. At least one of the three ligands (PRL, GH or PL) was expressed in 92.4% of the cases and they tend to be co-localized. Malignant tumours with epithelial PRL expression show shorter overall survival than tumours with no expression. The three ligands expression is higher in patients below 30 years old while the PRL-R expression is stronger in patients above 50 years old. In PEA1 cell line, PRL-R antagonism in combination with cisplatin shows decreased cell viability but not enhance apoptosis. The same effects are observed with the receptor knockdown with or without cisplatin. In PEO1 cell line, PRL-R antagonism in combination with cisplatin shows enhanced apoptosis, while PRL-R shRNA alone and in combination with cisplatin shows both decreased cell viability and enhanced apoptosis

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