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Id2 suppression of p15 counters TGF-beta-mediated growth inhibition of melanoma cells.counters TGF-beta-mediated growth inhibition of melanoma cells


Schlegel, N C; Eichhoff, O M; Hemmi, S; Werner, S; Dummer, R; Hoek, K S (2009). Id2 suppression of p15 counters TGF-beta-mediated growth inhibition of melanoma cells.counters TGF-beta-mediated growth inhibition of melanoma cells. Pigment Cell & Melanoma Research, 22(4):445-453.

Abstract

Proliferative resistance to transforming growth factor beta (TGF-beta) is regarded as a critical turning point in the malignant progression of many cancer types. In melanoma this resistance is associated with more aggressive metastatic behaviour. A recent study by our group identified proliferative and invasive subtypes of melanoma cultures and found that these are, respectively, susceptible and resistant to TGF-beta suppression of proliferation. Here, using previously characterised proliferative and invasive phenotype melanoma cultures, we explored molecular responses involved in modulating susceptibility to TGF-beta-mediated inhibition of proliferation. The Id2 gene was identified as being expressed more strongly in invasive phenotype cells less susceptible to TGF-beta repression than in proliferative phenotype cells. We correlated TGF-beta repression of Id2 gene expression in proliferative phenotype cells with p15(Ink4b) induction and cell cycle arrest. Furthermore, ectopic Id2 expression in proliferative phenotype cells counteracted p15(Ink4b) induction and consequently protected them from TGF-beta-mediated inhibition of proliferation. We conclude that transition to increased aggressiveness in melanoma cells requires Id2 upregulation to suppress TGF-beta induction of p15(Ink4b) and thus help to circumvent TGF-beta-mediated inhibition of proliferation.

Proliferative resistance to transforming growth factor beta (TGF-beta) is regarded as a critical turning point in the malignant progression of many cancer types. In melanoma this resistance is associated with more aggressive metastatic behaviour. A recent study by our group identified proliferative and invasive subtypes of melanoma cultures and found that these are, respectively, susceptible and resistant to TGF-beta suppression of proliferation. Here, using previously characterised proliferative and invasive phenotype melanoma cultures, we explored molecular responses involved in modulating susceptibility to TGF-beta-mediated inhibition of proliferation. The Id2 gene was identified as being expressed more strongly in invasive phenotype cells less susceptible to TGF-beta repression than in proliferative phenotype cells. We correlated TGF-beta repression of Id2 gene expression in proliferative phenotype cells with p15(Ink4b) induction and cell cycle arrest. Furthermore, ectopic Id2 expression in proliferative phenotype cells counteracted p15(Ink4b) induction and consequently protected them from TGF-beta-mediated inhibition of proliferation. We conclude that transition to increased aggressiveness in melanoma cells requires Id2 upregulation to suppress TGF-beta induction of p15(Ink4b) and thus help to circumvent TGF-beta-mediated inhibition of proliferation.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic
07 Faculty of Science > Institute of Molecular Life Sciences
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:August 2009
Deposited On:31 Jan 2010 17:56
Last Modified:05 Apr 2016 13:49
Publisher:Wiley-Blackwell
ISSN:1755-1471
Publisher DOI:https://doi.org/10.1111/j.1755-148X.2009.00571.x
PubMed ID:19368689
Permanent URL: https://doi.org/10.5167/uzh-28705

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