Antisense Smo under the control of the PTCH1 promoter delivered by an adenoviral vector inhibits the growth of human pancreatic cancer

Gao, Jun; Li, Z; Chen, Z; Shao, Jian-guo; Zhang, L; Gao, Xu; Tu, Zhenxing; Yang, Gong

doi:10.1038/sj.gt.3302816

Cited by 21 publications

(14 citation statements)

References 34 publications

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“…Consistent with recent published data (25)(26)(27)(28), our results revealed that expression of Hh signaling pathway-related molecules were at a higher level in the cancer tissues than in the matched adjacent non-tumor tissues and existed in all pancreatic cancer cell lines. Although pancreatic cancer tissue samples and cell lines expressed detectable levels of the mRNA of the molecules, the expression levels varied.…”

Section: Discussionsupporting

confidence: 92%

Hedgehog signaling pathway regulates human pancreatic cancer cell proliferation and metastasis

et al. 2012

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Abstract. Pancreatic cancer is one of the most aggressive and devastating malignancies. The Hedgehog (Hh) pathway has been reported to play an important role in pancreatic cancer development and progression. The aim of this study was to examine the activation of the Hh pathway in human pancreatic cancer tissue samples and pancreatic cancer cell lines, and the molecular mechanisms involved in the Hh pathway mediated effects on pancreatic cancer cell proliferation and invasion. The expression levels of Hh molecules in human pancreatic cancer tissue samples and pancreatic cancer cell lines were evaluated using RT-PCR. The role of the Hh pathway in cell proliferation and invasion was evaluated using flow cytometry, MTT, colony formation assays and Transwell invasion assays, and the expression of cancer stem cell markers and epithelial-mesenchymal transition (EMT) were evaluated using flow cytometry and RT-PCR. Tumorigenicity assays were used to further investigate the role of the Hh pathway in vivo. Hh molecules were highly expressed in human pancreatic cancer tissue samples and pancreatic cancer cell lines. Inhibition of the Hh pathway notably decreased cell proliferation and induced apoptosis through inhibition of the PI3K/AKT pathway and cancer stem cells. Furthermore, inhibition of the Hh signaling pathway significantly inhibited EMT by suppressing the activation of transcription factors Snail and Slug, which are correlated with significantly reduced pancreatic cancer cell invasion, suggesting that the Hh signaling pathway is involved in early metastasis. These results indicate that activation of the Hh pathway is a common event. Inhibition of the Hh pathway may be a potential molecular target of new therapeutic strategies for pancreatic cancer.

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Section: Discussionsupporting

confidence: 92%

Hedgehog signaling pathway regulates human pancreatic cancer cell proliferation and metastasis

et al. 2012

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“…The Hh signaling pathway is crucial in the growth and patterning during embryonic development, while abnormal activation of Hh signaling pathway is highly involved in tumor progression and metastasis [24,25]. As a tumor suppressor gene, PTCH1 inhibits tumor cell growth and motility by blocking the Hh signaling pathway [26]. PTCH1 is down-regulated in some malignant cancers, such as liver, breast, and esophageal cancer [27-29].…”

Section: Discussionmentioning

confidence: 99%

miR-212 promotes pancreatic cancer cell growth and invasion by targeting the hedgehog signaling pathway receptor patched-1

Nong

et al. 2014

J Exp Clin Cancer Res

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BackgroundmicroRNAs (miRNAs) are a class of small non-coding RNAs that play important roles in carcinogenesis. In the present study, we investigated the effect of miR-212 on pancreatic ductal adenocarcinoma (PDAC) and its target protein.MethodsQuantitative real-time PCR(qRT-PCR) was performed to detect the expression of miR-212 in PDAC tissues and pancreatic cancer cell lines. miR-212 mimic, miR-212 inhibitor and negative control were transfected into pancreatic cancer cells and the effect of miR-212 up-regulation and down-regulation on the proliferation, migration and invasion of cells were investigated. Furthermore, the mRNA and protein levels of Patched-1(PTCH1) were measured. Meanwhile, luciferase assays were performed to validate PTCH1 as miR-212 target in PDAC.ResultsmiR-212 was up-regulated in PDAC tissues and cells.Using both gain-of function and loss-of function experiments, a pro-oncogenic function of miR-212 was demonstrated in PDAC. Moreover, up-regulated of PTCH1 could attenuate the effect induced by miR-212.ConclusionThese data suggest that miR-212 could facilitate PDAC progression and metastasis through targeting PTCH1, implicating a novel mechanism for the progression of PDAC.

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“…Therefore, early detection of pancreatic cancer is the key for improving survival of patients. Unfortunately, no early-detection markers currently are available for early diagnosis of pancreatic cancer, although many scientists are pursuing pancreatic cancer research and believe that early detection of pancreatic cancer using molecular gene markers may be possible in the future [3,4]. …”

Section: Introductionmentioning

confidence: 99%

Methylation of the SPARC gene promoter and its clinical implication in pancreatic cancer

Gao

Song

Huang

et al. 2010

J Exp Clin Cancer Res

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BackgroundThe secreted protein acidic and rich in cysteine (SPARC) plays a pivotal role in regulating cell-matrix interactions and tumor angiogenesis, proliferation, and migration. Detection of SPARC gene methylation may be useful as a tumorigenesis marker for early detection of pancreatic cancer.MethodsMethylation of the SPARC gene transcriptional regulation region (TRR) was detected using bisulfite-specific (BSP) PCR-based sequencing analysis in 40 cases of pancreatic cancer and the adjacent normal tissues, 6 chronic pancreatitis tissues, and 6 normal pancreatic tissues. BSP cloning-based sequencing analysis was also performed in selected cases. Clinicopathological data from the cancer patients were collected and analyzed.ResultsAnalysis of SPARC gene TRR methylation showed two hypermethylation wave peak regions: CpG Region 1 (CpG site 1-7) and CpG Region 2 (CpG site 8-12). Pancreatic tissues have shown methylation in both regions with gradual increases from normal, chronic pancreatitis, and adjacent normal tissues to cancerous tissues. However, Methylation of CpG Region 2 was more sensitive than CpG Region 1 in pancreatic tumorigenesis. Furthermore, the methylation level of CpG Region 2 was associated with increased tumor size and exposure to the risk factors (tobacco smoke and alcohol consumption) for developing pancreatic cancer.ConclusionMethylation of the SPARC gene, specifically CpG Region 2, may be an early event during pancreatic tumorigenesis and should be further evaluated as a tumorigenesis marker for early detection of pancreatic cancer.

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Antisense Smo under the control of the PTCH1 promoter delivered by an adenoviral vector inhibits the growth of human pancreatic cancer

Cited by 21 publications

References 34 publications

Hedgehog signaling pathway regulates human pancreatic cancer cell proliferation and metastasis

Hedgehog signaling pathway regulates human pancreatic cancer cell proliferation and metastasis

miR-212 promotes pancreatic cancer cell growth and invasion by targeting the hedgehog signaling pathway receptor patched-1

Methylation of the SPARC gene promoter and its clinical implication in pancreatic cancer

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