Coexpression of growth arrest-specific gene 6 and receptor tyrosine kinases Axl and Sky in human uterine endometrial cancers.
BACKGROUND
Gas6, the protein product of the growth arrest-specific gene 6 (gas6), a member of the vitamin K-dependent protein family, was identified as a ligand for the Axl/Sky family of receptor tyrosine kinases. Gas6 acts as a growth-potentiating factor for thrombin-induced proliferation of vascular smooth muscle cells. The aim of the present study was to test for the presence of Gas6 and its receptors Axl and Sky, related to specific growth in uterine endometrial cancers, and to evaluate their plausible growth potential and mechanism.


METHODS
Sixty patients underwent curative resection for uterine endometrial cancers. In uterine endometrial cancers, the mRNA levels and histoscores of Gas6, Axl and Sky were determined by competitive RT-PCR using recombinant RNA and immunohistochemical studies, respectively. The rate of proliferation by immunochemistry for Ki67 and the rate of apoptosis by TUNEL were determined.


RESULTS
The mRNA levels and the histoscores of Gas6 and Axl in well-differentiated endometrial cancers (G1 EC) were significantly higher than in normal uterine endometrium (NE) and in moderately and poorly differentiated endometrial cancers (G2 + G3 EC). The rate of apoptosis in G1 EC was significantly lower than that in NE and in G2 + G3 EC.


CONCLUSIONS
Gas6 and Axl signal transduction is aberrantly stimulated in well-differentiated endometrial cancers, plausibly related to tumor progression due to protection from apoptosis in cancers cells.
Sun
W S
WS
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Gifu City, Japan.
Fujimoto
J
J
Tamaya
T
T
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D017209:Apoptosis; D001667:Binding, Competitive; D015139:Blotting, Southern; D015153:Blotting, Western; D016022:Case-Control Studies; D002455:Cell Division; D017931:DNA Primers / Q000737:chemistry; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029701:Saccharomyces cerevisiae Proteins; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6
D017931:DNA Primers; D036341:Intercellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; D015513:Oncogene Proteins; D010446:Peptide Fragments; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D020794:Receptor Protein-Tyrosine Kinases; D029701:Saccharomyces cerevisiae Proteins; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6; C490216:SKY1 protein, S cerevisiae; C000722289:AXL protein, human