The Setup Of Model System In Vitro And In Vivo For Functional Determination Of Oncogenic Effect Of Prolactin In Endometrial Cancer Development

Endometrial cancer is a common gynecological malignancy. The incidence is after cervical cancer. In recent years, the rate is still in a constant upward trend in worldwide. This trend deserves close attention from all sectors of society. Since the development of endometrial cancers is complex and diverse, the pathogenesis of endometrial cancer remains unclear as yet. It has seriously hampered the early diagnosis and treatment of endometrial cancer. Basic and clinical research have shown that the metabolism of human cells directly affect the development of the biological behavior. Most clinical research has been focus on cell metabolism about the risk factors in endometrial cancers. The expression of key genes and the biological role of key genes may be explain the abnormal proliferation of endometrial cancer, withered inhibition of cell death and other important aspects of metabolic regulation. Further explanation the pathogenesis of endometrial carcinoma can help us to make effective prevention and improve its prognosis.Prolactin is a neural-like polypeptide hormone discovered to be a pituitary factor .The mature form of the protein contains 199 amino acid residues. It is necessary for the mammary gland development and lactation, also stimulate to secrete of progesterone form luteal. Its structure is similar to growth hormone. There is increasing evidence that prolactin play an important role in breast, prostate and colorectal cancer via local production or accumulation. The multiplicity of prolactin actions in animals suggest its involvement in human pathophysiology.Eleavated levels of serum prolactin in endometrial cancers have been reported, suggesting that it may play a potential role in endometrial carcinogenesis. Pathological studies have shown the relationship between prolactin levels and prognosis of endometrial cancer. However, little research has been on the mechanism of secretion prolactin in endometrial cancer.Our experiments began with over-expression prolactin gene in endometrial carcinoma cell RL95-2 and ISHIKAWA, and use of RNA interference (RNAi) technology which could silence the expression of prolactin endometrial carcinoma cells. Sebsequenlty, reverse transcription-polymerase chain reaction (RT-PCR), Western blot, cell proliferation, apoptosis, clone formation assay and transwell technology was applied to explore the role of prolactin on endometrial cancer cells proliferation, apoptosis, invasion and migration in endometrial carcinoma cell. Combined use of severe combined immunodeficient-beige mice, explore the potential role for prolactin in endometrial tumorigenesis.The results show that over-expression of prolactin results in increased endometrial cancer cell proliferation, enhanced cell invasion and migration, also increased colony formation in soft agar. Prolactin can also significantly inhibit endometrial cancer cell apoptosis. Second, forced expression of prolactin increased tumor size in xenograft models . Third, RNA interference technology can effectively inhibit the levels of prolactin in endometrial cancer cells. The corresponding of inhibited cell proliferation, promoted apoptosis and a series of biological phenomena are emergenced.These indicate a potential role of prolactin in endometrial carcinogenesis. The studies therefore identify prolactin as a functionally and clinically validated molecule for targeted therapeutic development. It may offer a new vision for future research and treatment of endometrial cancer...