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Id2 suppression of p15 counters TGF‐β‐mediated growth inhibition of melanoma cells
Author(s) -
Schlegel Natalie C.,
Eichhoff Ossia M.,
Hemmi Silvio,
Werner Sabine,
Dummer Reinhard,
Hoek Keith S.
Publication year - 2009
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/j.1755-148x.2009.00571.x
Subject(s) - cancer research , transforming growth factor beta , melanoma , biology , downregulation and upregulation , cell growth , ectopic expression , phenotype , transforming growth factor , growth inhibition , cell culture , tgf beta signaling pathway , immunology , microbiology and biotechnology , gene , genetics
Summary Proliferative resistance to transforming growth factor β (TGF‐β) 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‐β suppression of proliferation. Here, using previously characterised proliferative and invasive phenotype melanoma cultures, we explored molecular responses involved in modulating susceptibility to TGF‐β‐mediated inhibition of proliferation. The Id2 gene was identified as being expressed more strongly in invasive phenotype cells less susceptible to TGF‐β repression than in proliferative phenotype cells. We correlated TGF‐β 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‐β‐mediated inhibition of proliferation. We conclude that transition to increased aggressiveness in melanoma cells requires Id2 upregulation to suppress TGF‐β induction of p15 Ink4b and thus help to circumvent TGF‐β‐mediated inhibition of proliferation.

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