Role of epidermal growth factor receptor overexpression, K-ras point mutation and c-myc amplification in the carcinogenesis of non-small cell lung cancer.

Sekine, Ikuo; Takami, Saki; Guang, Shao Guo; Yokose, Tomoyuki; Kodama, T; Nishiwaki, Yutaka; Kinoshita, M; Matsumoto, H.; Ogura, Tsutomu; Nagai, Kanji

doi:10.3892/or.5.2.351

Cited by 5 publications

(5 citation statements)

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“…Thus, the EGFR appears to play an important role in integrating environmental cues as diverse as cytokines, UV light, and extracellular matrix proteins (Sachsenmaier et al, 1994;Daub et al, 1996Daub et al, , 1997Moro et al, 1998;Li et al, 1999) to achieve regulation of cell migration, survival, and proliferation. The fine level of integration and orchestration of signaling performed by the EGFR is underscored by the tumorigenic effects caused by the aberrant expression and/or functioning of proteins at all levels of the EGFR-Ras-ERK signal transduction cascade (Gerosa et al, 1989;Ishitoya et al, 1989;Cook et al, 1992;Itakura et al, 1994;Mansour et al, 1994;Rajkumar and Gullick, 1994;Hirono et al, 1995;Normanno et al, 1995;Huang et al, 1996;Stumm et al, 1996;Bucci et al, 1997;Kuttan and Bhakthan, 1997;Sekine et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Integrin α5/β1 Mediates Fibronectin-dependent Epithelial Cell Proliferation through Epidermal Growth Factor Receptor Activation

Kuwada

2000

MBoC

138

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Human integrin alpha5 was transfected into the integrin alpha5/beta1-negative intestinal epithelial cell line Caco-2 to study EGF receptor (EGFR) and integrin alpha5/beta1 signaling interactions involved in epithelial cell proliferation. On uncoated or fibronectin-coated plastic, the integrin alpha5 and control (vector only) transfectants grew at similar rates. In the presence of the EGFR antagonistic mAb 225, the integrin alpha5 transfectants and controls were significantly growth inhibited on plastic. However, when cultured on fibronectin, the integrin alpha5 transfectants were not growth inhibited by mAb 225. The reversal of mAb 225-mediated growth inhibition on fibronectin for the integrin alpha5 transfectants correlated with activation of the EGFR, activation of MAPK, and expression of proliferating cell nuclear antigen. EGFR kinase activity was necessary for both MAPK activation and integrin alpha5/beta1-mediated cell proliferation. Although EGFR activation occurred when either the integrin alpha5-transfected or control cells were cultured on fibronectin, coprecipitation of the EGFR with SHC could be demonstrated only in the integrin alpha5-transfected cells. These results suggest that integrin alpha5/beta1 mediates fibronectin-induced epithelial cell proliferation through activation of the EGFR.

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Section: Discussionmentioning

confidence: 99%

Integrin α5/β1 Mediates Fibronectin-dependent Epithelial Cell Proliferation through Epidermal Growth Factor Receptor Activation

Kuwada

2000

MBoC

138

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“…Mapped to chromosome 12p12, Ras, 45 kb long, including four codon exons and 5' one uncondon exons, encodes p21 protein of 189 amino acids in length. Their mutations, which primarily affect codons 12, 13, and 61, lead to a constitutively active GTP-bound state and promote oncogenic activity by continually up-regulating downstream effector pathways [3] .…”

Section: Discussionmentioning

confidence: 99%

Relation between the Expression of K-ras in Hep-2 Cells and Development of Laryngeal Carcinoma

Xiong

Kong

Zhang

et al. 2006

Chinese-German J Clin Oncol

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Objective: To investigate the expression of K-ras in human laryngeal squamous cell carcinoma cell lines (Hep-2) and its significance for establishing a solid foundation for further study of the relationship between human laryngeal squamous cell carcinoma and K-ras gene point mutations. Methods:The expression of K-ras in human laryngeal squamous cell carcinoma cell lines (Hep-2) and human pancreatic carcinoma cell lines (MIAPaCa-2) was detected by using RT-PCR. Results: The expression of K-ras mRNA in Hep-2 and MIAPaCa-2 was strong and positive. Conclusion: The expression of K-ras mRNA in human laryngeal squamous cell carcinoma cell lines (Hep-2) is positive. Development of laryngeal carcinoma might be related to the activation of K-ras gene point mutation.

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“…In general, the activation of myc family oncogenes consists of augmented expression, which is often a result of gene amplification [25,26]. ras family oncogenes are predominantly activated by point mutations at amino acid positions 12, 13, or 61, which confer transforming activity to the ras protein [27].…”

Section: Discussionmentioning

confidence: 99%

“…In a wide variety of tumors, mutations of the c-K-ras gene occur most frequently. Specifically, mutations at codons 12 or 61 have been identified in the multistep process of tumor progression from normal to metastatic cells [26,27]. We used PCR amplification and dot blot analysis to investigate c-K-ras mutations in this tumor model ( fig.…”

Section: Discussionmentioning

confidence: 99%

c-K-<i>ras</i> Overexpression Is Characteristic for Metastases Derived from a Methylcholanthrene-Induced Fibrosarcoma

Algarra

Pérez²,

Serrano³

et al. 1998

Invasion Metastasis

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We investigated the relationship between the activation of the c-myc and c-K-ras proto-oncogenes and the acquisition of metastatic potential in a methylcholanthrene-induced BALB/c fibrosarcoma. The murine fibrosarcoma GR9 was originally induced in BALB/c mice following exposure to the carcinogenic chemical 3-methylcholanthrene. To induce spontaneous metastasis, we used two tumor cell clones (B9 and G2) known to differ in their metastatic potential, local tumor growth, H-2 class I expression and sensitivity to natural killer (NK) cells. The metastatic nodes were obtained from the lung, liver and kidney. The results showed: (1) amplification of the c-myc proto-oncogene in original tumor clones as well as in all metastatic nodes; (2) mRNA overexpression without amplification of the K-ras proto-oncogene in the metastatic cells, regardless of their anatomical location; (3) no c-K-ras point mutations at codons 12 and 61, and (4) in general, a statistically significantly reduced in vitro sensitivity of metastatic tumor cells to NK cells as compared with the tumor clones used to induce them (p < 0.05). These results therefore suggest that overexpressed c-K-ras mRNA is important during tumor progression, perhaps rendering metastatic tumor cells more resistant to lysis by NK cells.

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Role of epidermal growth factor receptor overexpression, K-ras point mutation and c-myc amplification in the carcinogenesis of non-small cell lung cancer.

Cited by 5 publications

References 0 publications

Integrin α5/β1 Mediates Fibronectin-dependent Epithelial Cell Proliferation through Epidermal Growth Factor Receptor Activation

Integrin α5/β1 Mediates Fibronectin-dependent Epithelial Cell Proliferation through Epidermal Growth Factor Receptor Activation

Relation between the Expression of K-ras in Hep-2 Cells and Development of Laryngeal Carcinoma

c-K-<i>ras</i> Overexpression Is Characteristic for Metastases Derived from a Methylcholanthrene-Induced Fibrosarcoma

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