Limits...
Transdifferentiation-inducing HCCR-1 oncogene.

Ha SA, Kim HK, Yoo J, Kim S, Shin SM, Lee YS, Hur SY, Kim YW, Kim TE, Chung YJ, Jeun SS, Kim DW, Park YG, Kim J, Shin SY, Lee YH, Kim JW - BMC Cell Biol. (2010)

Bottom Line: This MET occurring in HCCR-1 transfected cells is reminiscent of the transdifferentiation process during nephrogenesis.Indeed, expression of HCCR-1 was observed during the embryonic development of the kidney.Therefore, we propose that HCCR-1 may be a regulatory factor that stimulates morphogenesis of epithelia or mesenchyme during neoplastic transformation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Molecular Genetic Laboratory, Catholic Medical Research Institute, The Catholic University of Korea, Seoul, Korea.

ABSTRACT

Background: Cell transdifferentiation is characterized by loss of some phenotypes along with acquisition of new phenotypes in differentiated cells. The differentiated state of a given cell is not irreversible. It depends on the up- and downregulation exerted by specific molecules.

Results: We report here that HCCR-1, previously shown to play an oncogenic role in human cancers, induces epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) in human and mouse, respectively. The stem cell factor receptor CD117/c-Kit was induced in this transdifferentiated (EMT) sarcoma tissues. This MET occurring in HCCR-1 transfected cells is reminiscent of the transdifferentiation process during nephrogenesis. Indeed, expression of HCCR-1 was observed during the embryonic development of the kidney. This suggests that HCCR-1 might be involved in the transdifferentiation process of cancer stem cell.

Conclusions: Therefore, we propose that HCCR-1 may be a regulatory factor that stimulates morphogenesis of epithelia or mesenchyme during neoplastic transformation.

Show MeSH

Related in: MedlinePlus

HCCR-1 induced the c-kit proto-oncogene product. HCCR-1 induced the c-kit proto-oncogene product. A. Sections were stained for CD117. B. Western blot analysis to determine the expression of c-kit proto-oncogene product. HCCR-1 gene in embryonic kidney development.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2909153&req=5

Figure 2: HCCR-1 induced the c-kit proto-oncogene product. HCCR-1 induced the c-kit proto-oncogene product. A. Sections were stained for CD117. B. Western blot analysis to determine the expression of c-kit proto-oncogene product. HCCR-1 gene in embryonic kidney development.

Mentions: CD117 (c-Kit) is a type III receptor tyrosine kinase operating in cell signal transduction in several cell types. Normally c-Kit is activated (phosphorylated) by binding of its ligand, the stem cell factor (SCF) [15]. This leads to a phosphorylation cascade ultimately activating various transcription factors in different cell types. Such activation regulates apoptosis, cell differentiation, proliferation, chemotaxis, and cell adhesion. Ligand independent activation of c-Kit (dysregulated kit function) has been found to be an important component of oncogenesis in a large number of neoplastic disorders such as systemic mastocytosis, germ cell tumors, acute myelogenous leukemia (AML) with the disruption of the core binding factor, amongst others [16]. C-Kit positivity has been variably reported in sarcomas [16]. Among mesenchymal tumors, c-kit seems to be specific for the gastrointestinal stromal tumors (GISTs), which consistently express this protein. These tumors uniformly express CD117, the c-Kit proto-oncogene product [15]. Signal transductions from tyrosine kinase receptors have key roles in the regulation of cellular proliferation and differentiation [17] and binding of SCF to c-Kit activates multiple signal transduction pathways, including phosphatidylinositol 3-kinase (PI3K)/Akt [18]. Because HCCR-1 induced carcinosarcoma and HCCR-1 is regulated by the PI3K/Akt signaling pathway [19], we investigated whether HCCR-1-induced nude mice-derived carcinosarcoma induces the expression of CD117, as does GIST. HCCR-1-derived tumor cells showed a positive staining for CD117 (Figure 2A). Western blot analysis also showed that NIH/3T3 cells stably transfected with HCCR-1 and nude mice-derived tumors injected with NIH/3T3 cells transfected with HCCR-1 both overexpressed the c-kit protein compared with NIH/3T3 parental cells or cells transfected with vector alone (Figure 2B). Our study shows that HCCR-1-derived tumor cells express CD117, suggesting that HCCR-1 is related to the c-kit signaling pathway.


Transdifferentiation-inducing HCCR-1 oncogene.

Ha SA, Kim HK, Yoo J, Kim S, Shin SM, Lee YS, Hur SY, Kim YW, Kim TE, Chung YJ, Jeun SS, Kim DW, Park YG, Kim J, Shin SY, Lee YH, Kim JW - BMC Cell Biol. (2010)

HCCR-1 induced the c-kit proto-oncogene product. HCCR-1 induced the c-kit proto-oncogene product. A. Sections were stained for CD117. B. Western blot analysis to determine the expression of c-kit proto-oncogene product. HCCR-1 gene in embryonic kidney development.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2909153&req=5

Figure 2: HCCR-1 induced the c-kit proto-oncogene product. HCCR-1 induced the c-kit proto-oncogene product. A. Sections were stained for CD117. B. Western blot analysis to determine the expression of c-kit proto-oncogene product. HCCR-1 gene in embryonic kidney development.
Mentions: CD117 (c-Kit) is a type III receptor tyrosine kinase operating in cell signal transduction in several cell types. Normally c-Kit is activated (phosphorylated) by binding of its ligand, the stem cell factor (SCF) [15]. This leads to a phosphorylation cascade ultimately activating various transcription factors in different cell types. Such activation regulates apoptosis, cell differentiation, proliferation, chemotaxis, and cell adhesion. Ligand independent activation of c-Kit (dysregulated kit function) has been found to be an important component of oncogenesis in a large number of neoplastic disorders such as systemic mastocytosis, germ cell tumors, acute myelogenous leukemia (AML) with the disruption of the core binding factor, amongst others [16]. C-Kit positivity has been variably reported in sarcomas [16]. Among mesenchymal tumors, c-kit seems to be specific for the gastrointestinal stromal tumors (GISTs), which consistently express this protein. These tumors uniformly express CD117, the c-Kit proto-oncogene product [15]. Signal transductions from tyrosine kinase receptors have key roles in the regulation of cellular proliferation and differentiation [17] and binding of SCF to c-Kit activates multiple signal transduction pathways, including phosphatidylinositol 3-kinase (PI3K)/Akt [18]. Because HCCR-1 induced carcinosarcoma and HCCR-1 is regulated by the PI3K/Akt signaling pathway [19], we investigated whether HCCR-1-induced nude mice-derived carcinosarcoma induces the expression of CD117, as does GIST. HCCR-1-derived tumor cells showed a positive staining for CD117 (Figure 2A). Western blot analysis also showed that NIH/3T3 cells stably transfected with HCCR-1 and nude mice-derived tumors injected with NIH/3T3 cells transfected with HCCR-1 both overexpressed the c-kit protein compared with NIH/3T3 parental cells or cells transfected with vector alone (Figure 2B). Our study shows that HCCR-1-derived tumor cells express CD117, suggesting that HCCR-1 is related to the c-kit signaling pathway.

Bottom Line: This MET occurring in HCCR-1 transfected cells is reminiscent of the transdifferentiation process during nephrogenesis.Indeed, expression of HCCR-1 was observed during the embryonic development of the kidney.Therefore, we propose that HCCR-1 may be a regulatory factor that stimulates morphogenesis of epithelia or mesenchyme during neoplastic transformation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Molecular Genetic Laboratory, Catholic Medical Research Institute, The Catholic University of Korea, Seoul, Korea.

ABSTRACT

Background: Cell transdifferentiation is characterized by loss of some phenotypes along with acquisition of new phenotypes in differentiated cells. The differentiated state of a given cell is not irreversible. It depends on the up- and downregulation exerted by specific molecules.

Results: We report here that HCCR-1, previously shown to play an oncogenic role in human cancers, induces epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) in human and mouse, respectively. The stem cell factor receptor CD117/c-Kit was induced in this transdifferentiated (EMT) sarcoma tissues. This MET occurring in HCCR-1 transfected cells is reminiscent of the transdifferentiation process during nephrogenesis. Indeed, expression of HCCR-1 was observed during the embryonic development of the kidney. This suggests that HCCR-1 might be involved in the transdifferentiation process of cancer stem cell.

Conclusions: Therefore, we propose that HCCR-1 may be a regulatory factor that stimulates morphogenesis of epithelia or mesenchyme during neoplastic transformation.

Show MeSH
Related in: MedlinePlus