Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

p16INK4 gene, which encodes a specific inhibitor of cyclin-dependent kinase 4 (CDK4), has been recently reported as an important tumour suppressor gene. It is mapped to chromosome 9p21, which is frequently deleted or mutated in many tumour cell lines including malignant melanoma. Since the CDK4/cyclin D complex propels a cell to go through the G1 check point of the cell cycle, a critical phase of cell division, alteration of the p16INK4 gene could lead a cell to uncontrolled proliferation and malignant transformation. To clarify any role for p16INK4 and CDK4 proteins in the development of human malignant melanoma, we have examined, immunohistochemically, the expression of these two proteins in melanocytic neoplasms including 19 primary lesions of non-familial melanoma. Intense nuclear and/or cytoplasmic expression of the CDK4 protein was observed in 11 of 19 cases (58%) of melanoma. In contrast, virtually no nuclear or cytoplasmic staining for CDK4 protein was detected in 28 benign melanocytic naevi, including six Spitz naevi. Expression of p16INK4 protein was observed in three of 19 melanomas (16%) and in 17 of 28 benign naevi (61%). Inverse expression of CDK4 and p16INK4, at individual cell level, was detected in one case of melanoma. The present study suggests that CDK4 overexpression is characteristic for malignant melanoma, and probably reflects its autonomous accelerated cell proliferation. The expression rate of p16INK4 protein in malignant melanoma was lower than that in benign naevi, although the significance of p16INK4 deletion in melanoma development has not been definitely confirmed.
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PMID:Immunohistochemical detection of CDK4 and p16INK4 proteins in cutaneous malignant melanoma. 874 40

The cyclin-dependent kinase inhibitor p16 gene (P16, MTS1, CDKN2) has been shown to be altered by deletion or point mutation in some human tumours and cancer cell lines, suggesting that it works as a tumour suppressor. We analysed p16 gene mutation and p16 protein expression in 42 primary ovarian carcinomas and in five human ovarian cancer cell lines. Polymerase chain reaction (PCR) amplifications of exons 1 and 2 of the gene showed no deletion or gross rearrangement in the p16 gene. The lack of deletion was further demonstrated by Southern blot analysis. Looking for point mutations, we used single-strand confirmation polymorphism (SSCP) analysis and, in half of the tumours, we sequenced both strands of exons 1 and 2. No mutations were detected. In 11 out of 42 patients (26%), however, we detected no protein expression by Western blot analysis, suggesting that decreased expression of p16 rather than deletion of the gene can occur in a significant percentage of human ovarian cancers. In the same experiment CDK4 protein was found homogeneously expressed in all the tumour specimens and in the five cell lines. The lack of expression of p16 was not due to hypermethylation of the gene assessed by digestion of genomic DNAs with a methylation sensitive enzyme, suggesting that other mechanisms, not yet identified, are involved in the decreased expression of the p16 gene in human ovarian tumours.
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PMID:Absence of deletions but frequent loss of expression of p16INK4 in human ovarian tumours. 923 12