Intercellular Communication in Bronchial Epithelial Cells: Review of Evidence for a Possible Role in Lung Carcinogenesis

Albright, Craig D.; Jones, Raymond T.; Grimley, Philip M.; Resau, James H.

doi:10.1177/019262339001800211

Cited by 14 publications

(6 citation statements)

References 141 publications

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“…We and others have shown that Cx43 is undetectable in early stage human breast cancer tissue compared with adjacent normal tissue (Nicolson et al, 1988;Lee et al, 1992;Holden et al, 1997;Laird et al, 1999). Similar results are observed in other cancer tissues, such as ovarian cancer, lung cancer, and neuroblastomas (Albright et al, 1990;Tsai et al, 1996;Huang et al, 1999;Umhauer et al, 2000). This loss in Cx43 is believed to be among the earliest events by which transformed cells acquire independence from stimuli from neighboring cells.…”

supporting

confidence: 79%

Unexpected Induction of the Human Connexin 43 Promoter by the Ras Signaling Pathway Is Mediated by a Novel Putative Promoter Sequence

Carystinos¹,

Kandouz²,

Alaoui‐Jamali³

et al. 2003

Mol Pharmacol

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Connexin 43 (Cx43) is essential for survival and is tightly regulated at the transcriptional and post-transcriptional levels. A number of previous studies have demonstrated altered expression in malignant tissues, and in the presence of carcinogenic factors. We examined the effect of protooncogenes of Cx43 expression, and found no effect on Cx43 promoter activity in cells transformed with Src or erbB2. On the other hand, we identified and characterized a novel sequence that mediates Cx43 promoter regulation in cell lines engineered to overexpress H-Ras. Compared with wild-type NIH3T3 cells, both Cx43 mRNA and protein levels are increased in NIH3T3-Ras cells. The H-Rasϩ cells also have enhanced Cx43 promoter activation, which is inhibited by the MEK1 inhibitor 2Ј-amino-3Ј-methoxyflavone (PD98059), suggesting that Ras-mediated Cx43 overexpression is via the mitogen activated protein kinase kinase/extracellular signal-regulated pathway. Deletion analysis of the Cx43 promoter revealed a 200-bp region downstream of the Cx43 transcription start site as the minimal sequence essential for the Ras-mediated Cx43 up-regulation. Using this 200-base pair fragment in electrophoretic mobility shift assays, we identified one main protein complex that binds efficiently and is more abundant in nuclear extracts from NIH3T3-Ras and MCF7-Ras cells compared with their matched controls. This complex selectively recognizes a consensus sequence, AGTTCAATCA, located at positions ϩ149 to ϩ158 of the Cx43 promoter. Supershift assays identified the 90-kDa heat shock protein (HSP90) and c-Myc as constituents of this DNA-binding complex. Treatment of cells with the HSP90 inhibitor geldanamycin resulted in repression of the Cx43 promoter activity, and inhibits binding of the complex to the Cx43 promoter. Coimmunoprecipitation studies confirmed the interaction between endogenous HSP90 and c-Myc. This study provides evidence that the transcriptional up-regulation of Cx43 by Ras-Raf-MAPK is mediated via the interaction of a novel Cx43 promoter element with a protein complex that contains both HSP90 and c-Myc.

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supporting

confidence: 79%

Unexpected Induction of the Human Connexin 43 Promoter by the Ras Signaling Pathway Is Mediated by a Novel Putative Promoter Sequence

Carystinos¹,

Kandouz²,

Alaoui‐Jamali³

et al. 2003

Mol Pharmacol

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“…The direct physical contact between normal mesenchymal cells and lung carcinoma cells inhibited growth of malignant cells in vitro [87]. Co-culture of normal rat tracheal epithelial cells with chemically transformed tracheal epithelial cells suppressed the tumourigenicity of these cells upon inoculation into denuded tracheal grafts [88] [89]. The strong presence of these molecules in SCC and its normal distribution may be associated with the less frequent and late metastasis pattern of SCC as compared with adenocarcinoma.…”

Section: Cancer Cell-lung Epithelial Cell Interaction In Cancer Progrmentioning

confidence: 99%

“…Furthermore, factors physiologically released by bronchial epithelium such as TGF‐β, epidermal growth factor (EGF) and bombesin contribute to tumour growth . EGF and TGF‐β affect gap junction communication which is observed in tracheobronchial epithelium as these molecules can influence communication between epithelial cells during cancer growth . In comparison to bronchial epithelium, SCC secretes much more transforming growth factor α, and expressed greater numbers of cross‐reacting EGF receptors.…”

Section: Cancer Cell–lung Epithelial Cell Interaction In Cancer Progrmentioning

confidence: 99%

The role of the cell–cell interactions in cancer progression

Kamińska¹,

Szczylik²,

Bielecka

et al. 2015

J Cellular Molecular Medi

102

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In the field of cancer research, scientific investigations are based on analysing differences in the secretome, the proteome, the transcriptome, the expression of cell surface molecules, and the deregulation of signal transduction pathways between neoplastic and normal cells. Accumulating evidence indicates a crucial role in carcinogenesis concerning not only stromal cells but also normal cells from target organs and tissue where tumours emerge. The tumour microenvironment (TME) definitively plays an important role in regulating neighbouring cell behaviour. To date, limited attention has been focused upon interactions between cancer cells and normal cells. This review concentrates on the interactions between stromal and healthy cells from the TME in cancer development. In the article, the authors also describe mutations, genes and proteins expression pattern that are involved in tumour development in target organ.

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“…In mice, chemically induced lung tumors usually grow in solid or papillary patterns and originate from alveolar type I1 cells or bronchiolar Clara cells [12]. Both human NSCLC and SCLC have few intercellular junctions [13,141 and TGF-/3 and EGF modulate GJIC in normal and transformed human bronchial epithelial cells [15,IS]. The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, and airborne particulate matter reduced GJIC in primary cultures of rat alveolar type I1 cells [17].…”

mentioning

confidence: 99%

Role of Gap Junctions in Lung Neoplasia

Ruch

Cesen-Cummings

Malkinson

1998

Experimental Lung Research

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Reduced gap junctional intercellular communication (GJIC) has been noted in many types of neoplastic cells and may contribute to the neoplastic phenotype. This study assessed GJIC (by fluorescent dye-coupling) and gap junction protein (connexin) expression in mouse and human lung carcinoma cell lines and investigated whether reduced GJIC was involved in their neoplastic phenotype. Dye-coupling and connexin43 (Cx43) expression were much lower in most of the carcinoma lines (16 of 22) compared to nontransformed lung epithelial cells. Other connexins were not detected. A poorly communicating mouse lung carcinoma cell line (E9) was transfected with Cx43 or transduced with Cx32 and several stable clones were isolated that had 2- to 4-fold increased dye coupling. When evaluated for growth in vitro, the population doubling times were increased and the saturation densities were decreased in the clones. When assessed for tumorigenicity, the parental E9 cells formed tumors with a 100% incidence (6/6 mice), whereas the clones varied in tumorigenic response (0-88% incidence). The best communicating clone (E9-2) was not tumorigenic. The highly communicating Cx32 clone, E9/32-9, gave a tumor incidence of 88%. These results suggest that restoration of GJIC by forced connexin expression can reduce the growth and tumorigenicity of lung carcinoma cells in a connexin-specific manner.

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Intercellular Communication in Bronchial Epithelial Cells: Review of Evidence for a Possible Role in Lung Carcinogenesis

Cited by 14 publications

References 141 publications

Unexpected Induction of the Human Connexin 43 Promoter by the Ras Signaling Pathway Is Mediated by a Novel Putative Promoter Sequence

Unexpected Induction of the Human Connexin 43 Promoter by the Ras Signaling Pathway Is Mediated by a Novel Putative Promoter Sequence

The role of the cell–cell interactions in cancer progression

Role of Gap Junctions in Lung Neoplasia

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