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Overexpression Of PTEN Gene In Large Cells And Its Effection On Proliferation Of Cells

Posted on:2006-05-13Degree:DoctorType:Dissertation
Country:ChinaCandidate:C LouFull Text:PDF
GTID:1104360152996095Subject:Pathology and pathophysiology
Abstract/Summary:PDF Full Text Request
PTEN gene( named for its homology to phosphatases and tensin and the deletion of its gene on chromosome 10 in human cancers) encodes a 403-amino acid cytoplasmic protein with homology to the catalytic domain of tyrosine phosphatase and to the cytoskeletal protein tensin and auxilin. PTEN has been studied in recent years because of its function as a tumor suppressor in various advanced cancers. PTEN is inactivated by somatic mutation in increasing variety of malignant tumors both advanced and early stages, such as prostate carcinoma, glioblastoma, hepatocarcinoma, kidney carcinoma and endometrial carcinoma. In addition to a tumor suppressor, PTEN also took part in cells apoptosis, proliferation immigration and PI3K-AKT signal passway. More recently, it has been found that PTEN is closely related to cell size, especially to neuron enlargement and cardiomyocyte hypertrophy. PTEN has also involved in the control of tissue growth, such as Drosophila's eye cells and wings during Drosophila development, even in the enlargement of mice brain. The size of a cell critically depends on its DNA content. Second, cell size is stronglyinfluenced by the environment. Another determinant of cell size is temperature. Despite the long-standing interest in the phenomenon of cell-size control, the underlying genetic networks are still poorly understood.There are many different large cells in human normal tissues and tumors, such as osteoclast-like multinucleated giant cells in giant cell tumor of bone(GCT), oocytes in human ovary , Reed-Sternberg (R-S) cells in Hodgkin's lymphomas(HL), trophoblastic cells in human placenta and haematopoietic megakaryocyts in spleen with extramedullary haematopoiesis (SWEH) tissue. Does these large cells have relations with PTEN? To answer this question, we must make clear whether PTEN is expressed in these large cells first. PCR was used at first to detect the existence of PTEN gene in the whole tissues. Laser captured microdissection was used to isolate osteoclast-like multinucleated giant cells in GCT and oocytes in human ovaries, Exon-3 of PTEN was amplified by PCR. Then PTEN expression of mRNA and protein in these large cells weredetected by in situ hybridization and immunohistochemistry. The results are:(1) Exons-3,4,5 of PTEN gene were found by PCR in all of 8 GCT cases,5 ovary cases, 6 HL cases ,5 placenta cases and 1 SWEH case.(2)Exon-3 of PTEN gene was found in 4/ 10 GCT cases and in 1/1 ovary case after laser captured microdissection (3)Strong mRNA expression of PTEN was found only inosteoclast-like multinucleated giant cells in 23/27 GCT cases, in oocytes in 8/11 ovary cases, in R-S cells in 15/20 HL cases, in trophoblastic cells in 14/15 placenta cases and in haematopoietic megakaryocyt in 1/1 SWEH case . On the contrary, the small stromal cells or lymph cells around those large cells showednegative or weak PTEN mRNA expression.(4)The expression of PTEN protein was consistent with that of the PTEN mRNA , being detected only in...
Keywords/Search Tags:PTEN gene, large cell, cell size, overexpression, recombinant human bone morphogenetic protein-2, cell proliferation, laser captured microdissection
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