Cellular genes analogous to retroviral onc genes are transcribed in human tumour cells

Eva, Alessandra; Robbins, K C; Andersen, Philip R.; Srinivasan, Alagarsamy; Tronick, Steven R.; Reddy, E. Premkumar; Ellmore, Nelson; Galen, Angela T.; Lautenberger, James A.; Papas, Takis S.; Westin, Eric H.; Wong‐Staal, Flossie; Gallo, Robert C.; Aaronson, Stuart A.

doi:10.1038/295116a0

Cited by 488 publications

(182 citation statements)

References 42 publications

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“…Cell Culture-The 1A9 cell line is a clone of the human ovarian carcinoma cell line, A2780 (20). The two resistant sublines, 1A9PTX10 and 1A9PTX22, were isolated as individual clones in a single step selection, by exposing 1A9 cells to 5 ng/ml PTX in the presence of 5 g/ml verapamil, a Pgp antagonist.…”

Section: Methodsmentioning

confidence: 99%

Paclitaxel-resistant Human Ovarian Cancer Cells Have Mutant β-Tubulins That Exhibit Impaired Paclitaxel-driven Polymerization

Giannakakou¹,

Sackett²,

Kang³

et al. 1997

Journal of Biological Chemistry

641

583

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Section: Methodsmentioning

confidence: 99%

Paclitaxel-resistant Human Ovarian Cancer Cells Have Mutant β-Tubulins That Exhibit Impaired Paclitaxel-driven Polymerization

Giannakakou¹,

Sackett²,

Kang³

et al. 1997

Journal of Biological Chemistry

641

583

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“…[18][19][20][21][22] A2780 cells and their derivatives have been used frequently to model drug resistance in ovarian cancer. [23][24][25][26][27] They were cultured in the absence or presence of Epo for 24 hr (designated A2780 24hr cells) or for 2 months with refeeding and passaging as appropriate (designated A2780 2m35U and A2780 2m5U cells). For assay, the Epo was removed by washing the cells, and replicate cultures were grown in the absence of Epo and in the presence of specified concentrations of paclitaxel.…”

Section: Long-term Epo Treatment Leads To Increased Paclitaxel Resistmentioning

confidence: 99%

Erythropoietin treatment of human ovarian cancer cells results in enhanced signaling and a paclitaxel‐resistant phenotype

Solár

Feldman

Jeong

et al. 2007

Intl Journal of Cancer

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Erythropoietin (Epo), a glycoprotein hormone that is the principal regulator of erythropoiesis, is known to act also on nonhematopoietic cell types. Epo receptors have been reported on several normal and neoplastic human cells and tissues, including ovarian cancer cells. We found that long-term Epo treatment of A2780 cells resulted in the development of a phenotype exhibiting both enhanced Epo signaling, evidenced by increased peak levels of phospho-Erk1/2 and increased paclitaxel resistance. This phenotypic effect was specific for paclitaxel, since no change in cisplatin or carboplatin sensitivity was observed. In addition, the change in phenotype was stable, even after the removal of Epo. Measurement of mono-and oligonucleosome formation revealed that longterm Epo treated A2780 cells exhibited markedly less apoptosis than nonerythropoietin treated cells at essentially all concentrations of paclitaxel tested. Western blot analyses revealed that the long-term Epo treated cells had significantly reduced expression of apoptosis-related proteins Bcl-2 and Bcl-10. These findings may have implications for the clinical use of recombinant human Epo and other erythropoiesis stimulating agents to correct anemia in paclitaxel-treated cancer patients. ' 2007 Wiley-Liss, Inc.Key words: erythropoietin; signaling; ovarian cancer; paclitaxel; chemoresistance; apoptosis Erythropoietin (Epo) is the prime regulator of erythroid cell growth and differentiation. Additionally, a wide variety of normal and malignant nonhematopoietic cells have been reported to express the Epo receptor (EpoR) and in some cases, Epo has been shown to act on these cells, sometimes as a survival/antiapoptotic factor (reviewed in Ref. 1).Reports of erythropoietin receptor (EpoR) expression by a variety of cancer cell types and the use of recombinant human erythropoietin (epoetin) and darbepoetin to treat anemia in cancer patients have raised concern regarding the potential for antiapoptotic effects of these erythropoiesis stimulating agents on the cancer itself. [2][3][4][5][6] Some clinical studies have proven especially worrisome. The Breast Cancer Erythropoietin Trial (BEST) was terminated early because of increased mortality in patients receiving Epo. 6 There was an increase in early disease progression. A trial of Epo in head and neck cancer patients treated with radiotherapy resulted in an increase in locoregional recurrence and a decrease in survival in the Epo-treated group. 5 Recently, a trial of darbepoetin to enhance radiosensitivity of head and neck cancer was stopped due to a significantly poorer outcome in the darbepoetin treatment group. 7,8 In an accompanying study, we show that each of 4 human ovarian cancer cell lines, including A2780, expresses both the EpoR and Epo at the mRNA and protein levels. Additionally, we show that these EpoR are functional in initiating Epo-dependent intracellular signaling and that an Epo/EpoR autocrine/ paracrine mechanism may be operative in enhancing ovarian cancer cell growth.In the present report, we ha...

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“…Although expression of cellular oncogenes analogous to retroviral onc genes has been studied in fresh and culture derived human haematopoietic neoplastic cell types at various stages of differentiation and a variety of human cell lines (Westin et al, 1982a,b;Eva et al, 1982), similar studies on human solid tissues have not been reported. In this study we quantified the RNA transcripts from the Ki-ras, Ha-ras and sis human oncogene families from a series of premalignant adenomatous polyps and malignant tumours of the colorectum, normal colorectal mucosae and various established cell lines.…”

mentioning

confidence: 99%

Elevated expression of the human ras oncogene family in premalignant and malignant tumours of the colorectum

Spandidos¹,

Kerr²

1984

Br J Cancer

182

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Summary Study of expression of ras-related oncogenes in human premalignant polyps and malignant tumours of the colorectum, as well as in normal colorectal mucosa, shows a significant elevation in the premalignant and malignant tissues as compared to their respective colorectal mucosa. These results suggest that activation of the ras oncogene family occurs in the development of colorectal tumours and that elevated expression at a premalignant stage may well be critical in the process of carcinogenesis but not in itself sufficient.

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Cellular genes analogous to retroviral onc genes are transcribed in human tumour cells

Cited by 488 publications

References 42 publications

Paclitaxel-resistant Human Ovarian Cancer Cells Have Mutant β-Tubulins That Exhibit Impaired Paclitaxel-driven Polymerization

Paclitaxel-resistant Human Ovarian Cancer Cells Have Mutant β-Tubulins That Exhibit Impaired Paclitaxel-driven Polymerization

Erythropoietin treatment of human ovarian cancer cells results in enhanced signaling and a paclitaxel‐resistant phenotype

Elevated expression of the human ras oncogene family in premalignant and malignant tumours of the colorectum

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