Receptor for activated protein C kinase 1 (RACK1) is overexpressed in papillary thyroid carcinoma.
BACKGROUND
The receptor for activated C kinase 1 (RACK1) has been shown to be overexpressed in several types of cancers such as breast, colon, melanomas, and lung. RACK1 is linked to Ras-Raf-mediated signal transduction and transformed foci formation of 3T3 cells in vitro, and since this pathway is central in papillary thyroid carcinoma (PTC) oncogenesis, we hypothesized that RACK1 could play a role in the development or maintenance of PTC. No report on RACK1 expression in thyroid tissue is available; the present study was therefore aimed at identifying possible correlation of RACK1 expression at the mRNA or protein level in normal thyroid tissue compared to PTC.


METHODS
We used TaqMan quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry to study the RACK1 gene and protein expression in matched tumor and nontumor samples from 59 PTC patients. The tumor samples were divided into two main categories, low-risk (group 1-3) and high-risk (group 4-6), in accordance with both histological classification and clinical appearance.


RESULTS
RACK1 mRNA and protein levels were found highly overexpressed in tumor samples, whereas Ki-Ras mRNA was found to be relatively unchanged. B-Raf mRNA expression was low and detected only in tumor samples. Sequencing analysis detected no mutations in RACK1 or Ki-Ras, but 62.7% of the patients harbored the B-Raf single-nucleotide substitution T1799A (codon V600E). Phosphorylated extracellular signal-regulated kinase (pERK) immunohistochemistry analysis demonstrated activation of the mitogen-activated protein kinase (MAPK) pathway in tumor cells. Poorly differentiated and undifferentiated PTCs expressed significantly higher RACK1 mRNA levels than well-differentiated PTCs (p<0.017).


CONCLUSIONS
Taken together, our findings point to an important role of RACK1 protein in PTC development and progression. Our data also emphasize the importance of assessing protein expression and not only mRNA levels.
Department of Molecular Biology, University of Bergen, Bergen, Norway.
Line M
LM
Myklebust
Lars A
LA
Akslen
Jan Erik
JE
Varhaug
Johan R
JR
Lillehaug
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma; D002291:Carcinoma, Papillary; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
D009363:Neoplasm Proteins; C419368:RACK1 protein, human; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D048049:Extracellular Signal-Regulated MAP Kinases; D019204:GTP-Binding Proteins