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Hamid, Tariq; Malik, Mohammed T.; Kakar, Sham S.

doi:10.1186/1476-4598-4-3

Cited by 88 publications

(38 citation statements)

References 48 publications

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“…Some of the most highly connected genes within the MCM already have been identified as potential cancer targets (topoisomerase II␣, ARKB, PTTG1͞sercuin, Survivin, and EZH2) (23)(24)(25)(26)(27). To identify a potential novel gene target, we looked for the most highly connected genes that have not been extensively studied as cancer targets.…”

Section: Resultsmentioning

confidence: 99%

Analysis of oncogenic signaling networks in glioblastoma identifies ASPM as a molecular target

Horvath

Zhang²,

Carlson³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

603

585

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Glioblastoma is the most common primary malignant brain tumor of adults and one of the most lethal of all cancers. Patients with this disease have a median survival of 15 months from the time of diagnosis despite surgery, radiation, and chemotherapy. New treatment approaches are needed. Recent works suggest that glioblastoma patients may benefit from molecularly targeted therapies. Here, we address the compelling need for identification of new molecular targets. Leveraging global gene expression data from two independent sets of clinical tumor samples (n ‫؍‬ 55 and n ‫؍‬ 65), we identify a gene coexpression module in glioblastoma that is also present in breast cancer and significantly overlaps with the ''metasignature'' for undifferentiated cancer. Studies in an isogenic model system demonstrate that this module is downstream of the mutant epidermal growth factor receptor, EGFRvIII, and that it can be inhibited by the epidermal growth factor receptor tyrosine kinase inhibitor Erlotinib. We identify ASPM (abnormal spindle-like microcephaly associated) as a key gene within this module and demonstrate its overexpression in glioblastoma relative to normal brain (or body tissues). Finally, we show that ASPM inhibition by siRNA-mediated knockdown inhibits tumor cell proliferation and neural stem cell proliferation, supporting ASPM as a potential molecular target in glioblastoma. Our weighted gene coexpression network analysis provides a blueprint for leveraging genomic data to identify key control networks and molecular targets for glioblastoma, and the principle eluted from our work can be applied to other cancers. epidermal growth factor receptor vIII ͉ Glioblastoma ͉ modules ͉ weighted gene coexpression network analysis ͉ network-based screening

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Section: Resultsmentioning

confidence: 99%

Analysis of oncogenic signaling networks in glioblastoma identifies ASPM as a molecular target

Horvath

Zhang²,

Carlson³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

603

585

View full text Add to dashboard Cite

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“…Overexpression of human PTTG in mouse NIH3T3 fibroblasts and human embryonic kidney (HEK293) cells resulted in increased cell proliferation, induction of cells to form foci in monolayer culture and promotion of tumor formation in nude mice (24,26,27,72). These results clearly suggest that PTTG is a human oncogene.…”

Section: Tumorigenesismentioning

confidence: 86%

“…(176,177). In previous studies, we (72) showed that PTTG stimulates the expression of bFGF, VEGF and IL-8, which may Baltimore. Maryland) (89).…”

Section: Invasion Index Of Huvecmentioning

confidence: 88%

“…Collagenase activity was determined in tumor tissues extracted from nulnu mice as describe previously (72). Briefly, DQ collagen substrate (lmg/ml) was mixed with reaction buffer (0.5 M Tris-HCI, 1.5 M NaCl, 50 mM CaCh, 2 mM NaN 3 , pH 7.6) containing 0.8% low melting agarose (Invitrogen) at a ratio of 1: 1 as described by…”

Section: Transfection and Collection Of Conditioned Mediamentioning

confidence: 99%

“…Using iScript RT-PCR kit (Bio-Rad), first strand cDNA was synthesized and subsequently used for PCR amplification using the specific primers for MMP-2, MTI-MMP, PTTG, and GAPDH (72,163) (Table 3) using Taq polymerase (Takra Co.).…”

Section: Reverse Transcription-polymerase Chain Reaction (Rt -Per)mentioning

confidence: 99%

See 2 more Smart Citations

Regulation of angiogenic factors by pituitary tumor transforming gene (PTTG) in tumorigenesis.

Malik¹

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Gene expression profiling of pancreatic ductal adenocarcinomas in response to neoadjuvant chemotherapy

et al. 2023

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AimPancreatic ductal adenocarcinoma (PDAC) has the lowest survival rate of all major cancers. Chemotherapy is the mainstay systemic therapy for PDAC, and chemoresistance is a major clinical problem leading to therapeutic failure. This study aimed to identify key differences in gene expression profile in tumors from chemoresponsive and chemoresistant patients.MethodsArchived formalin‐fixed paraffin‐embedded tumor tissue samples from patients treated with neoadjuvant chemotherapy were obtained during surgical resection. Specimens were macrodissected and gene expression analysis was performed. Multi‐ and univariate statistical analysis was performed to identify differential gene expression profile of tumors from good (0%–30% residual viable tumor [RVT]) and poor (>30% RVT) chemotherapy‐responders.ResultsInitially, unsupervised multivariate modeling was performed by principal component analysis, which demonstrated a distinct gene expression profile between good‐ and poor‐chemotherapy responders. There were 396 genes that were significantly (p < 0.05) downregulated (200 genes) or upregulated (196 genes) in tumors from good responders compared to poor responders. Further supervised multivariate analysis of significant genes by partial least square (PLS) demonstrated a highly distinct gene expression profile between good‐ and poor responders. A gene biomarker of panel (IL18, SPA17, CD58, PTTG1, MTBP, ABL1, SFRP1, CHRDL1, IGF1, and CFD) was selected based on PLS model, and univariate regression analysis of individual genes was performed. The identified biomarker panel demonstrated a very high ability to diagnose good‐responding PDAC patients (AUROC: 0.977, sensitivity: 82.4%; specificity: 87.0%).ConclusionA distinct tumor biological profile between PDAC patients who either respond or not respond to chemotherapy was identified.

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Cited by 88 publications

References 48 publications

Analysis of oncogenic signaling networks in glioblastoma identifies ASPM as a molecular target

Analysis of oncogenic signaling networks in glioblastoma identifies ASPM as a molecular target

Regulation of angiogenic factors by pituitary tumor transforming gene (PTTG) in tumorigenesis.

Gene expression profiling of pancreatic ductal adenocarcinomas in response to neoadjuvant chemotherapy

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