Biomedical subjects

Hyewon Youn

Publications and source records attributed to Hyewon Youn.

3 recordsLinked to original sources

PubMed2006

Conditional Akt activation promotes androgen-independent progression of prostate cancer.

Aggressive androgen-independent (also termed as hormone-refractory) prostate cancer is a major clinical obstacle because there is no means to cure. Previous studies have shown that Akt activation is associated with prostate cancer progression from androgen-dependent to androgen-independent stage. However, its causative role in this process has not been established. One of the major limitations is the lack of a well-controlled inducible system to study Akt involvement. Recently, we developed a novel inducible Akt (iAKT) system based on a chemically induced dimerization (CID) approach. This system allows for conditional activation of Akt in a physiological setting. Utilizing this iAKT system, we found that Akt activation prevented cell death after serum withdrawal and promoted cell proliferation in the absence of androgen in vitro in human prostate cancer LNCaP cells, which should stop growing after androgen withdrawal or even die after serum starvation. The iAKT-induced death protection and growth promotion were further demonstrated in vivo using a transgenic mouse model that expresses the iAKT system conditionally in the prostate epithelium. Most importantly, in a mouse xenograft model derived from LNCaP cells, iAKT activation promoted tumor growth in castrated animals by enhancing cell proliferation and inhibiting apoptosis. Taken together, our data suggest that Akt activation is playing a causative role in androgen-independent progression of prostate cancer. This study provides a significant relevance of Akt-targeted therapy for hormone-refractory prostate cancers.

Androgens↗

PubMed2005

FAM20: an evolutionarily conserved family of secreted proteins expressed in hematopoietic cells.

BACKGROUND: Hematopoiesis is a complex developmental process controlled by a large number of factors that regulate stem cell renewal, lineage commitment and differentiation. Secreted proteins, including the hematopoietic growth factors, play critical roles in these processes and have important biological and clinical significance. We have employed representational difference analysis to identify genes that are differentially expressed during experimentally induced myeloid differentiation in the murine EML hematopoietic stem cell line. RESULTS: One identified clone encoded a previously unidentified protein of 541 amino acids that contains an amino terminal signal sequence but no other characterized domains. This protein is a member of family of related proteins that has been named family with sequence similarity 20 (FAM20) with three members (FAM20A, FAM20B and FAM20C) in mammals. Evolutionary comparisons revealed the existence of a single FAM20 gene in the simple vertebrate Ciona intestinalis and the invertebrate worm Caenorhabditis elegans and two genes in two insect species, Drosophila melanogaster and Anopheles gambiae. Six FAM20 family members were identified in the genome of the pufferfish, Fugu rubripes and five members in the zebrafish, Danio rerio. The mouse Fam20a protein was ectopically expressed in a mammalian cell line and found to be a bona fide secreted protein and efficient secretion was dependent on the integrity of the signal sequence. Expression analysis revealed that the Fam20a gene was indeed differentially expressed during hematopoietic differentiation and that the other two family members (Fam20b and Fam20c) were also expressed during hematcpoiesis but that their mRNA levels did not vary significantly. Likewise FAM20A was expressed in more limited set of human tissues than the other two family members. CONCLUSIONS: The FAM20 family represents a new family of secreted proteins with potential functions in regulating differentiation and function of hematopoietic and other tissues. The Fam20a mRNA was only expressed during early stages of hematopoietic development and may play a role in lineage commitment or proliferation. The expansion in gene number in different species suggests that the family has evolved as a result of several gene duplication events that have occurred in both vertebrates and invertebrates.

Amino Acid Sequence↗

PubMed2002

Mapping gene expression patterns during myeloid differentiation using the EML hematopoietic progenitor cell line.

OBJECTIVE: The detailed examination of the molecular events that control the early stages of myeloid differentiation has been hampered by the relative scarcity of hematopoietic stem cells and the lack of suitable cell line models. In this study, we examined the expression of several myeloid and nonmyeloid genes in the murine EML hematopoietic stem cell line. METHODS: Expression patterns for 19 different genes were examined by Northern blotting and RT-PCR in RNA samples from EML, a variety of other immortalized cell lines, and purified murine hematopoietic stem cells. Representational difference analysis (RDA) was performed to identify differentially expressed genes in EML. RESULTS: Expression patterns of genes encoding transcription factors (four members of the C/EBP family, GATA-1, GATA-2, PU.1, CBFbeta, SCL, and c-myb) in EML were examined and were consistent with the proposed functions of these proteins in hematopoietic differentiation. Expression levels of three markers of terminal myeloid differentiation (neutrophil elastase, proteinase 3, and Mac-1) were highest in EML cells at the later stages of differentiation. In a search for genes that were differentially expressed in EML cells during myeloid differentiation, six cDNAs were isolated. These included three known genes (lysozyme, histidine decarboxylase, and tryptophan hydroxylase) and three novel genes. CONCLUSION: Expression patterns of known genes in differentiating EML cells accurately reflected their expected expression patterns based on previous studies. The identification of three novel genes, two of which encode proteins that may act as regulators of hematopoietic differentiation, suggests that EML is a useful model system for the molecular analysis of hematopoietic differentiation.

3T3 Cells↗