Dataset Information

Association of chromosomal alterations with arsenite-induced tumorigenicity of human HaCaT keratinocytes in nude mice.

ABSTRACT: Inorganic arsenic is a well-documented human carcinogen. Chronic low-dose exposure to inorganic arsenic is associated with an increased incidence of a variety of cancers, including skin, lung, bladder, and liver cancer. Because genetic alterations often occur during cancer development, the objective of this study was to explore what types of genetic alterations were induced by chronic exposure of human HaCaT cells to arsenic. After 20 passages in the presence of inorganic trivalent arsenite at concentrations of 0.5 or 1 microM, HaCaT cells had higher intracellular levels of glutathione, became more resistance to arsenite, and showed an increased frequency of micronuclei. Furthermore, the previously nontumorigenic HaCaT cells became tumorigenic, as shown by subcutaneous injection into Balb/c nude mice. Cell lines derived from the tumors formed by injection of arsenite-exposed HaCaT cells into nude mice expressed higher levels of keratin 6, a proliferation marker of keratinocytes, than did parental HaCaT cells, whereas the expression of keratins 5, 8, and 10 was significantly decreased. Comparative genomic hybridization demonstrated chromosomal alterations in the 11 cell lines derived from these tumors; all 11 showed significant loss of chromosome 9q, and seven showed significant gain of chromosome 4q. The present results show that long-term exposure to low doses of arsenite transformed nontumorigenic human keratinocytes to cells that were tumorigenic in nude mice and that chromosomal alterations were observed in all cell lines established from the tumors.

SUBMITTER: Chien CW

PROVIDER: S-EPMC1253663 | biostudies-other | 2004 Dec

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Association of chromosomal alterations with arsenite-induced tumorigenicity of human HaCaT keratinocytes in nude mice.

Chien Chia-Wen CW Chiang Ming-Chang MC Ho I-Ching IC Lee Te-Chang TC

Environmental health perspectives 20041201 17

Inorganic arsenic is a well-documented human carcinogen. Chronic low-dose exposure to inorganic arsenic is associated with an increased incidence of a variety of cancers, including skin, lung, bladder, and liver cancer. Because genetic alterations often occur during cancer development, the objective of this study was to explore what types of genetic alterations were induced by chronic exposure of human HaCaT cells to arsenic. After 20 passages in the presence of inorganic trivalent arsenite at c ...[more]

PMID: 15579417

Similar Datasets

Project description:BackgroundKeratinocytes constitute a major part of the melanoma microenvironment, considering their protective role towards melanocytes in physiological conditions. However, their interactions with tumor cells following melanomagenesis are still unclear.MethodsWe used two in vitro models (melanoma-conditioned media and indirect co-culture of keratinocytes with melanoma cells on Transwell inserts) to activate immortalized keratinocytes towards cancer-associated ones. Western Blotting and qPCR were used to evaluate keratinocyte markers and mediators of cell invasiveness on protein and mRNA expression level respectively. The levels and activity of proteases and cytokines were analysed using gelatin-FITC staining, gelatin zymography, chemiluminescent enzymatic test, as well as protein arrays. Finally, to further study the functional changes influenced by melanoma we assessed the rate of proliferation of keratinocytes and their invasive abilities by employing wound healing assay and the Transwell filter invasion method.ResultsHaCaT keratinocytes activated through incubation with melanoma-conditioned medium or indirect co-culture exhibit properties of less differentiated cells (downregulation of cytokeratin 10), which also prefer to form connections with cancer cells rather than adjacent keratinocytes (decreased level of E-cadherin). While they express only a small number of cytokines, the variety of secreted proteases is quite prominent especially considering that several of them were never reported as a part of secretome of activated keratinocytes' (e.g., matrix metalloproteinase 3 (MMP3), ADAM metallopeptidase with thrombospondin type 1 motif 1). Activated keratinocytes also seem to exhibit a high level of proteolytic activity mediated by MMP9 and MMP14, reduced expression of TIMPs (tissue inhibitor of metalloproteinases), upregulation of ERK activity and increased levels of MMP expression regulators-RUNX2 and galectin 3. Moreover, cancer-associated keratinocytes show slightly elevated migratory and invasive abilities, however only following co-culture with melanoma cells on Transwell inserts.ConclusionsOur study offers a more in-depth view of keratinocytes residing in the melanoma niche, drawing attention to their unique secretome and mediators of invasive abilities, factors which could be used by cancer cells to support their invasion of surrounding tissues. Video abstract.

Dataset Information

Association of chromosomal alterations with arsenite-induced tumorigenicity of human HaCaT keratinocytes in nude mice.

Publications

Association of chromosomal alterations with arsenite-induced tumorigenicity of human HaCaT keratinocytes in nude mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets