The expression of p63 and p53 in keratoacanthoma and intraepidermal and invasive neoplasms of the skin

Sakiz, Damlanur; Türkmenoğlu, Tuğba Taşkın; Kabukçuoğlu, Fevziye

doi:10.1016/j.prp.2009.01.010

Cited by 34 publications

(43 citation statements)

References 18 publications

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“…QPCR analysis, which displays increased sensitivity for detecting low expression levels of isoforms, dem onstrated infrequent expression of TP63 isoforms in primary human melanocyte cultures but significantly elevated expres sion in >70% of established melanoma cell lines. In contrast with previous immunohistochemistry studies, which showed little or no expression of p63 protein (Brinck et al, 2002;Di Como et al, 2002;ReisFilho et al, 2003b;Dotto and Glusac, 2006;Bourne et al, 2008;Morgan et al, 2008;Sakiz et al, 2009;Kanner et al, 2010), our data provide the first evi dence of marked upregulation of both p63 mRNA and pro tein in melanoma cell lines.…”

Section: Depletion Of P63 Sensitizes Melanoma Cells To a Mitochondriacontrasting

confidence: 99%

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p63 is an alternative p53 repressor in melanoma that confers chemoresistance and a poor prognosis

Matin¹,

Chikh²,

Chong³

et al. 2013

J Cell Biol

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Section: Depletion Of P63 Sensitizes Melanoma Cells To a Mitochondriacontrasting

confidence: 99%

“…Expression of TAp63 and Np63 in uveal melanoma was dem onstrated in 12/18 (66.7%) and 1/18 (5.6%) cell lines, respec tively (Kilic et al, 2008). Other studies have suggested a lack of p63 expression in melanoma in situ or invasive disease Dotto and Glusac, 2006;Bourne et al, 2008;Morgan et al, 2008;Sakiz et al, 2009;Glusac, 2011).…”

mentioning

confidence: 92%

p63 is an alternative p53 repressor in melanoma that confers chemoresistance and a poor prognosis

Matin¹,

Chikh²,

Chong³

et al. 2013

J Cell Biol

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“…Elevated levels of DNp63a have been reported in a variety of SCC and BCC. 15,24,25 On the basis of the observations in Figure 5 that overexpression of DNp63a could repress nuclear PTEN, we next sought to determine whether the amplification of DNp63a seen in human non-melanoma cancers coincided with reduced nuclear PTEN. The expression and localization of p63 and PTEN was examined in normal skin cores (n ¼ 9), BCC cores (n ¼ 11) and SCC cores (n ¼ 11) using a tissue microarray ( Figure 6).…”

Section: Resultsmentioning

confidence: 99%

“…1,2,15,24,25 Skin-specific knockout of PTEN in mice leads to hyperproliferative and thickened skin. 27 The opposing phenotypes of PTEN and p63 in epidermal regulation suggested that these two proteins may integrate This proliferation is considered to be an important event for initiation and progression of prostate cancer and may occur in other cancers, such as non-melanoma skin cancers.…”

Section: Discussionmentioning

confidence: 99%

ΔNp63α regulates keratinocyte proliferation by controlling PTEN expression and localization

et al. 2011

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DNp63a, implicated as an oncogene, is upregulated by activated Akt, part of a well-known cell survival pathway. Inhibition of Akt activation by phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and the presence of putative p63-binding sites in the pten promoter led us to investigate whether DNp63a regulates PTEN expression. Knockdown of DNp63a led to increases in PTEN levels and loss of activated Akt, while overexpression of DNp63a decreased PTEN levels and elevated active Akt. The repression of PTEN by DNp63a occurs independently of p53 status, as loss of DNp63a increases PTEN expression in cell lines with and without functional p53. In addition, decreased levels of DNp63a resulted in an increase in nuclear PTEN. Conversely, in vivo nuclear PTEN was absent in the proliferative basal layer of the epidermis where DNp63a expression is highest. Additionally, we show that in keratinocytes a balance between DNp63a and PTEN regulates Akt activation and maintains normal proliferation rates. This balance is disrupted in non-melanoma skin cancers through increased DNp63a levels, and could enhance proliferation and subsequent neoplastic development. Our studies show that DNp63a negatively regulates PTEN, thereby providing a feedback loop between PTEN, Akt and DNp63a, which has an integral role in skin cancer development. Cell Death and Differentiation (2011) 18, 1924-1933 doi:10.1038/cdd.2011; published online 3 June 2011The p53 transcription factor family consists of the tumor suppressor p53 and the homologous p63 and p73. Unlike p53, p63 is essential for normal epidermal stratification and the proliferative potential of the epithelial stem cells. 1,2 p63 exists as various isoforms with contrasting functions. 2 The TA isoforms (TAp63a, TAp63b and TAp63g) have a full-length N-terminal transactivation domain, whereas the DN isoforms (DNp63a, DNp63b and DNp63g) have a short but distinct transactivation domain. All isoforms have a DNA-binding domain that shares high homology with p53 that allows p63 proteins to bind to p53 DNA-binding sites. 3,4 Similar to p53, the TA isoforms of p63 and p73 can promote apoptosis and growth arrest through the induction of antiproliferative genes. In contrast, the DN isoforms have been shown to induce pro-survival genes and inhibit anti-proliferative genes. [4][5][6] Several studies indicate that DNp63a, the predominant isoform in adult tissue, may function as an oncogene as it can exert a dominant-negative effect over p53 and the TAp63 and TAp73 isoforms. 2 Additionally, DNp63a is frequently overexpressed in a variety of squamous cell (SCC) and basal cell carcinomas (BCCs). 7,8 The survival factor Akt can increase DNp63a levels and in turn, DNp63a protects against UV-B-induced apoptosis via Akt activation. 9,10 However, the mechanism behind the positive feedback loop between DNp63a and Akt has not been described. Akt activation can be negated by phosphatase and tensin homolog deleted on chromosome 10 (PTEN). PTEN dephosphorylates phosphatidylinositol 3,4,5-trisphosphate, thereby...

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“…Nie wykazano korelacji pomiędzy ekspresją p53 i p63, co sugeruje ich niezależną funkcję w procesie kancerogenezy w obrębie skóry [37].…”

Section: Ekspresja I Przydatność Diagnostyczna P63 W Nowotworach Skóryunclassified

The role of p63 proteins in tumorigenesis and the significance of their expression in the diagnosis of skin and female genital tract neoplasms

Wysocka-Dubielecka¹,

Majewski²,

Loza³

2015

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STRESZCZENIEProteiny p63 są homologami białka p53 i razem z p73 tworzą rodzinę białek p53, która obejmuje czynniki transkrypcyjne regulujące metabolizm, proliferację, różnicowanie, starzenie się i śmierć komórki. Białko p63 odgrywa znaczącą rolę w rozwoju i funkcjonowaniu naskórka i innych nabłonków płaskich oraz ma znaczenie w procesie kancerogenezy. p63 występuje w wielu izoformach zaliczanych do 2 głównych grup: TAp63 oraz ΔNp63. TAp63 są produkowane w bardzo małych stężeniach (z wyjątkiem oocytów). ΔNp63 stanowią dominującą izoformę i wystę-pują głównie w podstawnych komórkach nabłonkowych skóry, przydatków, piersi, prostaty i układu moczowego. W przeciwieństwie do TAp63, formy ΔN uznaje się za onkoproteiny. W żeńskim układzie rozrodczym p63 może mieć duże znaczenie w diagnostyce problematycznych raków, gdy rozpoznanie decyduje o dalszym postępowaniu terapeutycznym. Białka p63 biorą też udział w aktywacji transkrypcji późnych genów HPV podczas proliferacji i różnicowania komórek nabłonkowych. Proteiny p63 coraz częściej są wykorzystywane w diagnostyce nowotworów skóry, układu rozrodczego, sutka, głowy i szyi oraz płuc.ABSTRACT p63 proteins are p53 homologs, and with p73 belong to the p53 family. These transcription factors regulate metabolism, proliferation, differentiation, aging and cell death. p63 is crucial for development and maintenance of squamous epithelium, and plays an important role in cancerogenesis. p63 exists in multiple isoforms belonging to 2 main groups: TAp63 and ΔNp63. TAp63 are expressed at very low levels (except for oocytes). ΔNp63 isoforms are predominant isoforms overexpressed in basal epithelial cells of skin, appendages, breast, prostate, and urinary tract. In contrast to TAp63, they are believed to act as oncoproteins. In the female genital tract p63 may be a very useful marker for distinguishing problematic cancers, when diagnosis determines the therapeutic management. It seems that p63 is necessary for activation of HPV late gene expression upon epithelial proliferation and differentiation. p63 is increasingly being taken into account in the diagnosis of epithelial tumors of skin, genital tract, breast, head, neck and lungs.Rola białek p63 w kancerogenezie oraz znaczenie ich ekspresji w diagnostyce nowotworów skóry i żeńskiego układu rozrodczegoThe role of p63 proteins in tumorigenesis and the significance of their expression in the diagnosis of skin and female genital tract neoplasms

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The expression of p63 and p53 in keratoacanthoma and intraepidermal and invasive neoplasms of the skin

Cited by 34 publications

References 18 publications

p63 is an alternative p53 repressor in melanoma that confers chemoresistance and a poor prognosis

p63 is an alternative p53 repressor in melanoma that confers chemoresistance and a poor prognosis

ΔNp63α regulates keratinocyte proliferation by controlling PTEN expression and localization

The role of p63 proteins in tumorigenesis and the significance of their expression in the diagnosis of skin and female genital tract neoplasms

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