Carcinogenesis of PIK3CA

German, Sidra; Aslam, Hafiz Muhammad; Saleem, Saima; Raees, Aisha; Anum, Tooba; Alvi, Arsalan Ahmad; Haseeb, Abdul

doi:10.1186/1897-4287-11-5

Cited by 30 publications

(23 citation statements)

References 21 publications

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“…These agents are currently being tested in clinical trials, both as single agents and in combination with other treatments [30,35] (Table 3).…”

Section: The Pi3k/akt/mtor Pathwaymentioning

confidence: 99%

“…Numerous mutations or alterations in the PI3K pathway have now been identified in human SCCHN, at the level of both gene expression and function (Table 2) [29]. These genes include, but are not limited to: PIK3CA, PIK3CD, PTEN, PDK1, AKT, and mTOR [8,[30][31][32][33][34][35]. Mutations and copy number alterations of PI3K pathway components, including PIK3CA amplifications and PTEN inactivation by loss or inactivation of gene copy, are particularly prevalent in HPV-positive tumors [36].…”

Section: The Pi3k/akt/mtor Pathwaymentioning

confidence: 99%

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Targeting the PI3K/AKT/mTOR pathway in squamous cell carcinoma of the head and neck

2015

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“…These agents are currently being tested in clinical trials, both as single agents and in combination with other treatments [30,35] (Table 3).…”

Section: The Pi3k/akt/mtor Pathwaymentioning

confidence: 99%

Section: The Pi3k/akt/mtor Pathwaymentioning

confidence: 99%

Targeting the PI3K/AKT/mTOR pathway in squamous cell carcinoma of the head and neck

2015

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“…These ligands include epidermal growth factor (EGF) or VEGF. Somatic mutations in cancer cells only occur in PIK3CA and PI3KR1, which encodes the p85 α subunit (3,6,9). These mutations are concentrated in two key regions of the PIK3CA gene, consisting of the helical domain of exon 9 and the kinase domain of exon 20 (7,8,10).…”

Section: Introductionmentioning

confidence: 99%

“…EGFR triggers a downstream signalling cascade through, for example, the Kirsten rat sarcoma viral oncogene homolog-serine/threonine-protein kinase B-Raf and the phosphatidylinositol 3-kinase (PI3K), catalytic subunit α-phosphatase and tensin homolog-Akt pathways, which regulate cell proliferation, survival, apoptosis resistance, invasion and migration (2,3,(5)(6)(7)(8). The PIK3CA gene encodes the p110α subunit of PI3K α and belongs to class IA of the PI3Ks.…”

Section: Introductionmentioning

confidence: 99%

Mutation of the PIK3CA gene as a prognostic factor in patients with colorectal cancer

et al. 2015

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Abstract. Colorectal cancer (CRC) is one of the most common cancers worldwide, with ~700,000 mortalities occurring due to CRC in 2012. The treatment options are effective in a small percentage of patients, and it is important to identify specific biomarkers in order to determine patients for whom the available therapies will be beneficial. It has been hypothesised that the PIK3CA gene mutation may affect the response to therapy of patients with metastatic CRC. In the present study, primary tumour specimens were collected from 156 patients with CRC who were treated in the Military Institute of Medicine in Warsaw (Warsaw, Poland). Codons 12 and 13 of exon 1 of KRAS, exons 11 and 15 of BRAF and exons 9 and 20 of PIK3CA were analysed for mutation using direct sequencing. The prognostic value of each mutation and the clinical and pathological variables of these tumours were estimated. The results revealed that PIK3CA mutations were present in 15 patients (9.6%), of whom seven (46.7%) possessed mutations in codon 9 and eight (53.3%) possessed mutations in codon 20. Mutation in the PIK3CA gene was detected in six patients with KRAS gene mutations, which accounted for 40% of PIK3CA-mutated tumours, and in one patient with BRAF mutations, which accounted for 6.6% of PIK3CA-mutated tumours. No significant differences were identified between the overall survival (OS) rates of patients with PIK3CA mutations (median OS, 56.7 months) and those with wild-type PIK3CA genes (median OS, 47.6 months) (P=0.1270). Univariate analysis identified that the following prognostic factors affected the OS rate in the current patient cohort: Gender, female patients survived for 57.5 months compared with 39.3 months for male patients (P=0.0111); and lymph node involvement grade, as survival of patients without lymph node metastases was 61.4 months compared with 45.4 months in patients presenting with metastases (P= 0.0122). The findings of the present analysis indicate that PIK3CA mutation status is not a prognostic factor in CRC patients. In addition, no statistically significant association exists between tumours with PIK3CA mutations and clinical or pathological factors.

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“…Studies by Carnero A et al 2008 have indicated that a class of HDAC protein SIRT1 is required for PI3K mediated cancer cell growth. 5,6 PI3K/Akt /mTOR signaling can reduce p53 response through inhibitory effect on its stability. 7 Tumor suppressor gene p53 plays a crucial role in executing anti-proliferative effects such as growth arrest, apoptosis and cell senescence, in response to various types of stress.…”

Section: Introductionmentioning

confidence: 99%

Bisindole-PBD regulates breast cancer cell proliferation via SIRT-p53 axis

Sarma

Bag

Ramaiah

et al. 2015

Cancer Biology & Therapy

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In a previous study we reported the role of potent bisindole-PBD conjugate as an inclusion in the arsenal of breast cancer therapeutics. In breast cancer cell proliferation, PI3K/AKT/mTOR pathway plays a crucial role by prosurvival mechanism that inhibits programmed cell death. Here, 2 breast cancer cells lines, MCF-7 and MDA-MB-231 were treated with Vorinostat (suberoylanilide hydroxamic acid / SAHA) and bisindole-PBD (5b). We have investigated the effect on PI3K/AKT/mTOR pathway and SIRT expression including epigenetic regulation. There was consistent decrease in the level of PI3K, AKT, mTOR proteins upon treatment of 5b in both MCF-7 and MDA-MB-231 cell lines compared to untreated controls. Treatment with caspase inhibitor (Q-VD-OPH) confirmed that the effect of 5b on PI3K signaling was ahead of apoptosis. Real time PCR and western blot analysis showed profound reduction in the mRNA and protein levels of SIRT1 and SIRT2. Molecular docking studies also supported the interaction of 5b with various amino acids of SIRT2 proteins. Treatment with 5b caused epigenetic changes that include increase of acetylated forms of p53, increase of histone acetylation at p21 promoter as well as decrease in methylation state of p21 gene. Compound 5b thus acts as SIRT inhibitor and cause p53 activation via inhibition of growth factor signaling and activation of p53 dependent apoptotic signaling. This present study focuses bisindole-PBD on epigenetic alteration putting 5b as a promising therapeutic tool in the realm of breast cancer research.

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Carcinogenesis of PIK3CA

Cited by 30 publications

References 21 publications

Targeting the PI3K/AKT/mTOR pathway in squamous cell carcinoma of the head and neck

Targeting the PI3K/AKT/mTOR pathway in squamous cell carcinoma of the head and neck

Mutation of the PIK3CA gene as a prognostic factor in patients with colorectal cancer

Bisindole-PBD regulates breast cancer cell proliferation via SIRT-p53 axis

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