Establishment and antitumor effects of dasatinib and PKI-587 in BD-138T, a patient-derived muscle invasive bladder cancer preclinical platform with concomitant EGFR amplification and PTEN deletion

Chang, Nakho; Lee, Hye Won; Lim, Ji Hyun; Jeong, Da Eun; Song, Hye Jin; Kim, Sudong; Nam, Do‐Hyun; Sung, Hyun Hwan; Jeong, Byong Chang; Seo, Seong Il; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han-Yong; Jeon, Hwang Gyun

doi:10.18632/oncotarget.10539

Cited by 9 publications

(6 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, they showed that dasatinib suppresses the growth of RT112 parental cells, whilst dasatinib enhances the invasive tumor growth of RT112 gemcitabine-resistant cells in vivo. 38 Although other groups also suggested the use of dasatinib for bladder cancer patients, 39,40 it is known that tyrosine kinase activity and expression of c-Src is elevated in low-grade bladder cancer lesions, whereas high-grade cancers display decreased expression and kinase activity. 41,42 Therefore, we need to consider the possibility of dasatinib treatment for bladder cancer patients carefully.…”

Section: Discussionmentioning

confidence: 99%

Glycoprotein nonmetastatic melanoma protein B impacts the malignant potential of bladder cancer cells through its hem‐immunoreceptor tyrosine‐based activation motif

Kimura,

Okita,

Nagumo

et al. 2024

Pathology International

View full text Add to dashboard Cite

Bladder cancer is one of the most common cancers among men worldwide. Although multiple genomic mutations and epigenetic alterations have been identified, an efficacious molecularly targeted therapy has yet to be established. Therefore, a novel approach is anticipated. Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a type I transmembrane glycoprotein that is highly expressed in various cancers. In this study, we evaluated bladder cancer patient samples and found that GPNMB protein abundance is associated with high‐grade tumors, and both univariate and multivariate analyses showed that GPNMB is a prognostic factor. Furthermore, the prognosis of patients with high GPNMB levels was significantly poorer in those with nonmuscle invasive bladder cancer (NMIBC) than in those with muscle invasive bladder cancer (MIBC). We then demonstrated that knockdown of GPNMB in MIBC cell lines with high GPNMB inhibits cellular migration and invasion, whereas overexpression of GPNMB further enhances cellular migration and invasion in MIBC cell lines with originally low GPNMB. Therefore, we propose that GPNMB is one of multiple driver molecules in the acquisition of cellular migratory and invasive potential in bladder cancers. Moreover, we revealed that the tyrosine residue in the hemi‐immunoreceptor tyrosine‐based activation motif (hemITAM) is required for GPNMB‐induced cellular motility.

show abstract

Section: Discussionmentioning

confidence: 99%

Glycoprotein nonmetastatic melanoma protein B impacts the malignant potential of bladder cancer cells through its hem‐immunoreceptor tyrosine‐based activation motif

Kimura,

Okita,

Nagumo

et al. 2024

Pathology International

View full text Add to dashboard Cite

show abstract

“…The PTEN gene plays an important carcinostatic effect in a variety of tumor cells. Studies have shown that the PTEN gene is inactivated in a variety of malignant tumors (such as bladder cancer, prostate cancer, endometrial cancer and gastric cancer) due to deletion, mutation, or reduced transcription [ 13 – 16 ]. PTEN has phosphatase activity.…”

Section: Discussionmentioning

confidence: 99%

Effect of CTP-mediated PTEN on 5637 bladder cancer cells and the underlying molecular mechanism

Yuan

Yang

et al. 2022

BMC Urol

View full text Add to dashboard Cite

Objective The aim of the present study was to explore the effect of cytoplasmic transduction peptide (CTP)-phosphatase and tensin homolog (PTEN) on the proliferation, cell cycle, apoptosis, migration and invasion of bladder cancer cells and the underlying molecular mechanism. Methods A eukaryotic expression vector, pTT5-CTP-PTEN, was constructed. The constructed vector was transfected into HEK 293-6E cells to express a fusion protein, CTP-PTEN. The fusion protein was purified. 5637 bladder cancer cells were cocultured with purified CTP-PTEN fusion protein. Target gene expression, protein expression, cell proliferation, cell cycle, apoptosis, cell invasion and cell migration were examined by reverse transcription polymerase chain reaction (RT-PCR), western blot, MTT assay, flow cytometry, Transwell assay, and cell scratch assay, respectively. Results Both PTEN and CTP-PTEN fusion protein inhibited the proliferation, cell cycle, invasion and migration of bladder cancer cells and promoted the apoptosis of bladder cancer cells. The effect of CTP-PTEN was more significant. Conclusions The fused expression of CTP and PTEN significantly increased the penetrability of the tumor suppressor gene PTEN into cancer cells. The CTP-PTEN fusion protein exhibited a significant carcinostatic effect on 5637 bladder cancer cells.

show abstract

“…In certain patients with advanced BC, loss of PTEN activity is observed ( 29 ). PTEN is a tumor suppressor gene that negatively regulates cell proliferation and survival and reduction of PTEN induces constitutive phosphorylation of the AKT/PKB signaling pathway, thereby enhancing cancer cell cycle progression, survival and migration in BC patients ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

Enhanced plasma miR‑26a‑5p promotes the progression of bladder cancer via targeting PTEN

Wang

Chen

2018

Oncol Lett

View full text Add to dashboard Cite

The current study aimed to evaluate the expression and specific role of miR-26a-5p in the progression of bladder cancer (BC). Reverse transcription-quantitative polymerase chain reaction analysis was performed to evaluate the level of miR-26a-5p in BC cancer and healthy controls. The present data showed that plasma miR-26a-5p was significantly increased in BC patients. Furthermore, BC tissues exhibited greater levels of miR-26a-5p compared with adjacent non-neoplastic tissues-26a-5p. Compared with BC patients at Ta-T1 stage, the level of miR-26a-5p was significantly elevated in BC patients ≥T2. BC patients at G3 stage demonstrated a higher plasma miR-26a-5p level compared with those at G1/2 stage. Receiver operating characteristic (ROC) analysis indicated that miR-26a-5p could differentiate BC patients from controls. Additionally, Kaplan-Meier analysis demonstrated that plasma miR-26a-5p negatively correlated with survival of BC patients. Dual luciferase reporter assay indicated that miR-26a-5p significantly suppressed the relative luciferase activity of pmirGLO-PTEN-3′UTR compared with the control. In conclusion, the current study indicated novel data that the levels of plasma miR-26a-5p was significantly increased in BC patients. Furthermore, the present study suggested that determination of plasma miR-26a-5p level could help to distinguish BC patients from healthy controls via targeting PTEN.

show abstract

Establishment and antitumor effects of dasatinib and PKI-587 in BD-138T, a patient-derived muscle invasive bladder cancer preclinical platform with concomitant EGFR amplification and PTEN deletion

Cited by 9 publications

References 64 publications

Glycoprotein nonmetastatic melanoma protein B impacts the malignant potential of bladder cancer cells through its hem‐immunoreceptor tyrosine‐based activation motif

Glycoprotein nonmetastatic melanoma protein B impacts the malignant potential of bladder cancer cells through its hem‐immunoreceptor tyrosine‐based activation motif

Effect of CTP-mediated PTEN on 5637 bladder cancer cells and the underlying molecular mechanism

Enhanced plasma miR‑26a‑5p promotes the progression of bladder cancer via targeting PTEN

Contact Info

Product

Resources

About