Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

p53 homologue, p51/p63, predominantly expressed in keratinocyte stem cells, is indispensable for the formation of epidermis. Notch1, another such gene indispensable for the process, induces growth arrest and differentiation in keratinocytes. We found that exogenous expression of DeltaNp51B (DeltaNp63alpha), one of the isoforms of p51 specifically expressed in basal keratinocytes, blocked Notch 1-dependent growth arrest and differentiation in mouse keratinocytes by inhibiting p21 expression and maintaining integrins expression. Furthermore, DeltaNp51B by itself was found to have ability to induce expression of integrin alpha6beta4, which promotes attachment of basal cells to basal membrane thereby keeping the cells in immature state. Therefore, we conclude that DeltaNp51B expression warrants integrin expression even under the influence of Notch1 and that DeltaNp51B is a long-sought factor required to maintain basal cell keratinocytes immaturity by inhibiting Notch1 activity. We will postulate a plausible model explaining the maintenance of the squamous epithelium architectures as well as offering mechanistic explanations for pathological features of skin diseases, including cancers, psoriasis along with physiological wound healings.
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PMID:p53 homologue, p51/p63, maintains the immaturity of keratinocyte stem cells by inhibiting Notch1 activity. 1723 12

Oral squamous cell carcinomas (OSCCs) are described as the result of a multistep tumorigenesis process. In order to develop useful diagnosis of pre-malignant lesions, expression of p53 family members and the cancer stem cell (CSCs) marker, CD44v6, were studied in histologically normal oral epithelium, precancerous lesions and succeeding invasive OSCCs. p53 was expressed focally in normal epithelium adjacent to tumors, while expression was high in intra-epithelial neoplasia and moderate in OSCC. p63 nuclear staining was important in basal and suprabasal layers of histologically normal oral mucosa and in immature compartments of premalignant lesions and cancer. In epithelium without neoplasia, intense p73 staining was observed in the basal layer, while focal expression was present in suprabasal layers. Most immature dysplastic areas showed either high or moderate staining, whereas those in OSCCs expressed low and moderate p73 level expression. CD44v6 was only expressed in poorly differentiated areas of epithelium, altered or not. p53, p63 and p73 positive stainings were statistically related in intra-epithelial neoplasia to tumours. Analysis of TP53 mutations in 17% of tumours principally revealed G>A and A>G transitions. No relation was observed between this mutational profile and different immunostainings. In conclusion, our results support that immunostaining of p53 family members might be helpful in diagnosis and monitoring of high-risk pre-malignant lesions of oral epithelium. The combination of staining patterns of p63, p73alpha and CD44v6 enabled us to isolate phenotypic undifferentiated or transient amplifying areas, reflecting the immaturity of the tumour cell lineage. While CD44v6 expression is an interesting marker of such epithelial cells, it is not specific enough to be useful alone and other phenotypic markers are needed.
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PMID:Expression of p53 family members and CD44 in oral squamous cell carcinoma (OSCC) in relation to tumorigenesis. 2005 5