PTEN can inhibit in vitro organotypic and in vivo orthotopic invasion of human bladder cancer cells even in the absence of its lipid phosphatase activity

Gildea, John J; Herlevsen, Mikael; Harding, Michael A.; Gulding, Kathryn M; Moskaluk, Christopher A.; Frierson, Henry F.; Theodorescu, Dan

doi:10.1038/sj.onc.1207599

Cited by 76 publications

(57 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As with other solid tumors, the activation of oncogenes and the abnormal expression of tumor suppressor genes are considered the main reasons for the occurrence of osteosarcoma (18). Previous studies have revealed that PTEN inhibits the proliferation, invasion and metastasis of tumor cells (19)(20)(21). The mutation and deletion of the PTEN gene have been confirmed to occur in osteosarcoma in dogs, where, in 60% of osteosarcoma cells, PTEN gene expression was suppressed or the gene was deleted (22).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of miRNA‑21 attenuates the proliferation and metastasis of human osteosarcoma by upregulating PTEN

Miu

et al. 2017

Exp Ther Med

View full text Add to dashboard Cite

Abstract. The present study aimed to investigate the expression of micro (mi)RNA-21 in osteosarcoma cells, and its role in inhibiting the invasion and metastasis of osteosarcoma. Human osteosarcoma MG-63 cells and osteoblast hFOB1.19 cells were used to compare the expression of miRNA-21 using reverse transcription-quantitative polymerase chain reaction analysis. A miRNA-21 mimic or inhibitor were transfected into the MG-63 cells to upregulate and downregulate the expression of miRNA-21, respectively. The present study investigated the proliferation and invasion of transfected MG-63 cells using MTT and Transwell assays. Western blot analyses were used to investigate the regulation of important proteins in the phosphatase and tensin homolog/phosphoinositide 3-kinase/RAC-α serine/threonine-protein kinase (PTEN/PI3K/AKT) signaling pathway. Compared with hFOB1.19 cells, miRNA-21 expression was significantly upregulated in the MG-63 cells (P<0.01), which lead to increased proliferation. Downregulating miRNA-21 expression reduced the proliferation of MG-63 cells compared with hFOB1.19 cells. Invasion assays and western blot analyses revealed that the overexpression of miRNA-21 significantly enhanced the invasion ability of MG-63 cells and the expression of phosphorylated (p-)AKT, while downregulation of miRNA-21 expression reduced the protein level of AKT and p-AKT. In the MG-63 cells, miRNA-21 upregulation significantly inhibited the protein level of PTEN, resulting in significantly increased AKT and PI3K protein levels (P<0.01). In conclusion, the results of the present study indicate that the expression of miRNA-21, PI3K and AKT is increased in the osteosarcoma cell line MG-63, which results in reduced expression of PTEN and increased expression of proteins in the PI3K/AKT signaling pathway, and thus increases the aggressiveness of osteosarcoma cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibition of miRNA‑21 attenuates the proliferation and metastasis of human osteosarcoma by upregulating PTEN

Miu

et al. 2017

Exp Ther Med

View full text Add to dashboard Cite

show abstract

“…The role of PTEN in negatively regulating cell migration is probably the reason why PTEN can suppress tumor invasion and metastasis. Indeed, in a human bladder cancer cell line with a functionally impaired PTEN, it was found that transfection of wild-type PTEN inhibited both soft agar colony formation and cancer cell invasion, whereas transfection of the G129E mutant inhibited cancer cell invasion but failed to suppress colony formation, indicating a role for lipid phosphatase activity and protein phosphatase activity in inhibiting cell growth and cell migration, respectively [20]. The putative protein phosphatase activity of PTEN might also regulate the cell cycle, because the G129E mutant retains the capability to arrest cell cycle of MCF-7 cells as wildtype PTEN, while the G129R and H123Y mutants (they lack both phosphatase activities as the C124S mutant) do not [21].…”

Section: Pten As a Tumor Suppressor And Master Cellular Regulatormentioning

confidence: 99%

PTEN: a default gate-keeping tumor suppressor with a versatile tail

Wang

Jiang

2008

Cell Res

View full text Add to dashboard Cite

The tumor suppressor PTEN controls a variety of biological processes including cell proliferation, growth, migration, and death. As a master cellular regulator, PTEN itself is also subjected to deliberated regulation to ensure its proper function. Defects in PTEN regulation have a profound impact on carcinogenesis. In this review, we briefly discuss recent advances concerning PTEN regulation and how such knowledge facilitates our understanding and further exploration of PTEN biology. The carboxyl-tail of PTEN, which appears to be associated with multiple types of posttranslational regulation, will be under detailed scrutiny. Further, a comparative analysis of PTEN and p53 suggests while p53 needs to be activated to suppress tumorigenesis (a dormant gatekeeper), PTEN is probably a constitutive surveillant against cancer development, thus a default gatekeeper.

show abstract

“…10,11,14 Six-week-old nude mice were purchased from National Cancer Institute (Bethesda, MD) and were maintained under University of Virginia Animal Care and Use Committee guidelines. To generate cell lines with propensity for liver metastasis, mice were injected with 1 ϫ 10 6 T24T cells in 100 l of serum-free Dulbecco's modified Eagle's medium into the splenic capsule.…”

Section: Derivation Of Metastatic Cell Lines and Crossed Site Experimmentioning

confidence: 99%

Profiling Bladder Cancer Organ Site-Specific Metastasis Identifies LAMC2 as a Novel Biomarker of Hematogenous Dissemination

Smith

Nicholson

Nitz

et al. 2009

The American Journal of Pathology

Self Cite

View full text Add to dashboard Cite

Little is known about which genes mediate metastasis in bladder cancer, which accounts for much of the mortality of this disease. We used human bladder cancer cell lines to develop models of two clinically common metastatic sites, lung and liver, and evaluated their gene expression with respect to human tumor tissues. Parental cells were injected into either the murine spleen to generate liver metastases or tail vein to generate lung metastases with sequential progeny derived by re-injection and comparisons made of their organ-specific nature by crossed-site injections. Both genomic and transcriptomic analyses of organselected cell lines found salient differences and shared core metastatic profiles, which were then screened against gene expression data from human tumors. The expression levels of laminin V gamma 2 (LAMC2) contained in the core metastatic signature were increased as a function of human tumor stage, and its genomic location was in an area of gain as measured by comparative genomic hybridization. Using immunohistochemistry in a human bladder cancer tissue microarray, LAMC2 expression levels were associated with tumor grade, but inversely with nodal status. In contrast, in node-negative patients, LAMC2 expression was associated with visceral metastatic recurrence. In summary, LAMC2 is a novel biomarker of bladder cancer metastasis that reflects the propensity of cells to metastasize via either lymphatic or hematogenous routes. Metastasis represents a critical event in the natural history of disease for a cancer patient and is associated with significant reduction in patient survival.1 However, although a significant body of research has shed light on this process, less is known about the nature of organspecific metastasis.2,3 In vivo metastasis assays using cancer cell lines passaged through mouse models have been used to discover the role of specific genes relevant to metastatic behavior. 4 For example, in breast cancer, recent reports have addressed the question of the molecular regulation of organ site-specific metastasis. Using the spontaneously metastatic MDA-MB-231 human breast cancer cell line, one group reported the in vivo selection of sublines of differing metastatic potential to bone, lung, and adrenal gland, 5,6 and then evaluated in both animal models and metastatic tumor tissues from patients the gene expression profiles associated with site-specific metastasis. 7Bladder cancer is the fifth most commonly diagnosed cancer in the United States, 8 and the molecular lesions characterizing bladder carcinogenesis and progression are beginning to be better elucidated. 9 However, little is known about the pathways that regulate general metastatic propensity or organ site-specific tropism to lung or liver, which are two common sites of dissemination in this and other tumor types. Our prior work has focused on the discovery and investigation of genes that regulate lung metastasis, such as the metastasis suppressor RhoGDI2, by comparing metastatic T24T cells to their isogenic nonmetastatic relativ...

show abstract

PTEN can inhibit in vitro organotypic and in vivo orthotopic invasion of human bladder cancer cells even in the absence of its lipid phosphatase activity

Cited by 76 publications

References 32 publications

Inhibition of miRNA‑21 attenuates the proliferation and metastasis of human osteosarcoma by upregulating PTEN

Inhibition of miRNA‑21 attenuates the proliferation and metastasis of human osteosarcoma by upregulating PTEN

PTEN: a default gate-keeping tumor suppressor with a versatile tail

Profiling Bladder Cancer Organ Site-Specific Metastasis Identifies LAMC2 as a Novel Biomarker of Hematogenous Dissemination

Contact Info

Product

Resources

About