Overexpression of the G-protein inwardly rectifying potassium channel 1 (GIRK1) in primary breast carcinomas correlates with axillary lymph node metastasis.
The acquisition of genetic alterations in tumor cells is a hallmark of cancer progression. Genetic alterations, including chromosomal sequence alterations and abnormal gene expression, increase the malignant potential of tumors by affecting pathways that regulate cell growth, cell death, tumor angiogenesis, and invasion/metastasis. We used an expression profiling technique, representational difference analysis, to identify genes the expressions of which are aberrantly increased in invasive breast carcinomas as compared with adjacent normal breast tissue from the same individual. Among the genes we identified was GIRK1, which encodes a 501 amino acid, G-protein inwardly rectifying potassium channel protein. We then measured GIRK1 mRNA expression in benign breast tissues, primary invasive breast carcinomas, and metastatic breast carcinomas from axillary lymph nodes using quantitative TaqMan reverse transcription-PCR and correlated the results with clinical parameters. We found that GIRK1 overexpression correlated with lymph node metastasis (P < 0.0029), and overexpression was greatest in tumors with more than one positive lymph node. These results indicate that GIRK1 may be useful as a biomarker for lymph node metastasis and possibly a pharmaceutical target.
Stringer
B K
BK
Department of Pathology, Faulkner Hospital, Boston, Massachusetts 02130, USA. bstringer@faulknerhospital.org
Cooper
A G
AG
Shepard
S B
SB
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D020224:Expressed Sequence Tags; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008875:Middle Aged; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D015221:Potassium Channels / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D018076:DNA, Complementary; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D012313:RNA