Mutations of the PH domain of protein kinase B (PKB/AKT) are absent in human epidermal skin tumors.
BACKGROUND
While for most human solid tumors genetic alterations of few distinct genetic regions have been found, studies on basal cell carcinomas (BCC) have shown the prevalence of several abnormalities including alterations of the three ras genes, GAP (GTPase activating protein), p53, PTCH (the human homologue of Drosophila patched) and SMOH (the human homologue of Drosophila smoothened). On the other hand, during the last decade, a new oncogene, protein kinase B (PKB/AKT), has been characterized and found to be overexpressed in certain human tumors. In vivo activation of PKB/AKT necessitates its recruitment to the cell membrane mediated by the N-terminal pleckstrin homology (PH) domain.


OBJECTIVE
We investigated whether mutations of this mandatory domain are present in a subset of human epidermal skin tumors.


METHODS
RNA of 19 human skin tumors including 13 BCC, 4 squamous cell carcinomas (SCC; including 1 keratoacanthoma) and 2 neurofibromas of different size and tumor stage were used for reverse transcription and subsequent PCR amplification of the PH domain of PKB/AKT.


RESULTS
Cycle sequencing of the purified PCR products did not reveal any mutation of the PH domain of PKB/AKT.


CONCLUSIONS
In human BCC and SCC, mutations of the PH domain of PKT/AKT do not play a major role during the carcinogenesis of these tumors.
Waldmann
V
V
Department of Dermatology, University of Heidelberg, Germany.
Wacker
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002280:Basal Cell Carcinoma / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009455:Neurofibroma / Q000235:genetics*; D017354:Point Mutation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D012878:Skin Neoplasms / Q000235:genetics*
D011518:Proto-Oncogene Proteins; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt