Altered expression and function of beta1 integrins in a highly metastatic human lung adenocarcinoma cell line.

Takenaka, Kiyoshi; Shibuya, Masabumi; Takeda, Yuichiro; Hibino, Suguru; Gemma, Akihiko; Ono, Yasushi; Kudoh, Shoji

doi:10.3892/ijo.17.6.1187

Cited by 38 publications

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“…PC9/f9 (Takenaka et al, 2000) and PC9/f14 (Gemma et al, 2001) are highly metastatic sublines of PC9 established at Nippon Medical School using artificial metastasis methods. In an attempt to elucidate potential mechanisms of resistance to gefitinib, we evaluated cDNA expression profiles and their relationship to gefitinib resistance.…”

Section: Cell Linesmentioning

confidence: 99%

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Reduction of PTEN protein and loss of epidermal growth factor receptor gene mutation in lung cancer with natural resistance to gefitinib (IRESSA)

et al. 2005

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Gefitinib (IRESSA), an epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitor, has antitumour activity in the advanced non-small-cell lung cancer (NSCLC) setting. However, in chemotherapy-naïve patients with advanced NSCLC, the addition of gefitinib to standard chemotherapy regimens failed to increase survival. These results suggest the need for improved patient selection and combination rationales for targeted therapies. We have identified subpopulations of an adenocarcinoma cell line that are naturally resistant to gefitinib, and have analysed the cDNA expression profiles, genomic status of EGFR gene and the effect of gefitinib on signalling pathways in these cell lines in order to identify key mechanisms for naturally acquired resistance to gefitinib. Gefitinib-resistant subpopulations demonstrated increased Akt phosphorylation (not inhibited by gefitinib), reduced PTEN protein expression and loss of the EGFR gene mutation when compared with parental cell lines. These differences in Akt and PTEN protein expression were not evident from the cDNA array profiles. These data suggests that (1) the EGFR gene mutation may be possibly lost in some cancer cells with other additional mechanisms for activating Akt, (2) reintroduction of PTEN or pharmacological downregulation of the constitutive PI3K -Akt-pathway activity may be an attractive therapeutic strategy in cancers with gefitinib resistance.

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Section: Cell Linesmentioning

confidence: 99%

“…cells in nude mice and subsequent culture of the tumour cells harvested from pulmonary metastatic foci (Takenaka et al, 2000). PC9/f14 was established by five additional inoculations (Gemma et al, 2001).…”

Section: Effect Of Gefitinib On Cell Growth In Vitromentioning

confidence: 99%

Reduction of PTEN protein and loss of epidermal growth factor receptor gene mutation in lung cancer with natural resistance to gefitinib (IRESSA)

et al. 2005

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“…The altered integrins can change affinity and avidity for their extracellular matrix (ECM), and cancer cells become more adhesive and invasive, and lead to increased metastatic potential and enhanced angiogenic potential (Hood et al, 2002). In previous study, robust associations between altered α5β1-integrin expression and highly metastatic potential was revealed in human lung adenocarcinoma cell line (Takenaka et al, 2000). In the current study, we found that α5β1-integrin expression in cervical cancer tissues (143/169, 84.6%) remarkably higher than the corresponding normal mucosa (23/68, 33.8%), and there was statistically significant difference (χ 2 = 59.616, P < 0.001).…”

Section: Relationship Between α5β1-integrin and Overall Survival Of Cmentioning

confidence: 99%

Prognostic Significance of α5β1-integrin Expression in Cervical Cancer

Wang¹,

Chen²,

Wang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Asian Pacific J Cancer Prev, 14 (6), 3891-3895 IntroductionCervical cancer (CC) is the second most common malignant diseases of women in the world. More than 500,000 new cases of cervical cancer were reported each year worldwide, of which approximately 1/3 from China mainland. So, cervical cancer is a cause of significant morbidity and cancer-related mortality in China women. With the improvement of modern irradiation techniques and development of novel drugs, cervical cancer remains an unsolved problem of oncology both due to the increased rate of local failures and of the distant metastasis. Although the death rate for cervical cancer has decreased dramatically since the introduction of cervical cytology as a widespread screening procedure, the survival rate at advanced stages of disease has not improved. Therefore, characterization of identifiable molecular markers may play an important role in understanding of molecular pathogenesis and in identifying latently prognostic biomarkers for cervical cancer.Numerous studies demonstrated that α5β1-integrin expression levels are altered in many types of cancer (Morozevich et al., 2009), there may be involved in modulating effect on several signalling pathways ,which are closely related to the regulation of cell survival, proliferation ,differentiation and apoptosis, and in stimulating tumor angiogenesis (Zeng et al., 2009) Although it has been shown that α5β1-integrin AbstractThe purpose of this study was to evaluate the association of expression of α5β1-integrin with clinicopathologic features and prognosis in cervical cancer. Levels of α5β1-integrin in normal cervical mucosa and cervical cancer tissue were detected with immunohistochemistry. Survival analysis by the Kaplan-Meier method was performed to assess prognostic significance. α5β1-integrin expression was detected in 84.6% (143/169) cervical cancer samples, significantly different from that in normal cervical mucosa (P < 0.05). Positive expression rates of α5β1-integrin in patients with poor histologic differentiation, lymph node metastasis, and recurrence were elevated. Using Kaplan-Meier analysis, a comparison of survival curves of low versus high expression of α5β1-integrin revealed a highly significant difference in human cervical cancer cases (P < 0.05), suggesting that overexpression of α5β1-integrin is associated with a worse prognosis.The α5β1-integrin promotes angiogenesis and associates with lymph node metastasis, vascular invasion and poor prognosis of cervical cancer. The current study indicated that α5β1-integrin may be an independent prognostic factor for cervical cancer patients.

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“…beta 1D, 20 catenin beta 1, 21,22 platelet/endothelial cell adhesion molecule (CD31 antigen), 23,24 and paxillin 25 was decreased in pathologic Stage IA NSCLC specimens. The loss of these cell adhesion molecules might be related to local and distant metastasis.…”

Section: Discussionmentioning

confidence: 99%

cDNA microarray analysis of gene expression in pathologic stage IA nonsmall cell lung carcinomas

Nakamura

Saji

Ogata

et al. 2003

Cancer

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BACKGROUNDThe relationship between altered gene expression and tumor progression in lung carcinoma has yet to be characterized. Gene expression in pathologic Stage IA nonsmall cell lung carcinoma specimens was analyzed using a cDNA microarray.METHODSSurgical specimens were used for the current study. The pathologic stage was IA (AJCC) in five tumors, IB in two, IIA in one, IIIA in one, and IIIB in one. Seven tumor specimens were adenocarcinomas and three were squamous cell carcinomas. Paired mRNAs from carcinoma cells and normal lung tissue specimens from the same lobe were labeled with different fluorochromes during cDNA probe synthesis in a reverse‐transcription reaction. Both synthesized, labeled cDNA probes were mixed and hybridized to the microarray. The signal intensity of each spot was measured by laser scanner and gene expression was quantified as the tumor‐to–normal fluorescence ratio (T:N ratio). The gene was overexpressed when the T:N ratio was greater than 2.0 and underexpressed when the ratio was less than 0.5.RESULTSOverall, 40 (9.4%) of the 425 genes evaluated were overexpressed, and 74 genes (17.4%) were underexpressed. In the 5 Stage IA tumor specimens, 31 (7.3%) genes were overexpressed and 76 (17.9%) were underexpressed. For 30 genes (7.1%), expression was different in Stage IA tumor specimens compared with more advanced tumor specimens.CONCLUSIONSThe cDNA microarray system showed that numerous alterations of gene expression were present in early‐stage nonsmall cell lung carcinoma specimens. Cancer 2003;97:2798–805. © 2003 American Cancer Society.DOI 10.1002/cncr.11406

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Altered expression and function of beta1 integrins in a highly metastatic human lung adenocarcinoma cell line.

Cited by 38 publications

References 0 publications

Reduction of PTEN protein and loss of epidermal growth factor receptor gene mutation in lung cancer with natural resistance to gefitinib (IRESSA)

Reduction of PTEN protein and loss of epidermal growth factor receptor gene mutation in lung cancer with natural resistance to gefitinib (IRESSA)

Prognostic Significance of α5β1-integrin Expression in Cervical Cancer

cDNA microarray analysis of gene expression in pathologic stage IA nonsmall cell lung carcinomas

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