MUC4 interacts with ErbB2 in human gallbladder carcinoma: potential pathobiological implications.
Muc4 interacts with erbB2 and potentiates tumourigenesis and/or tumour growth. The expression of MUC4, the interaction of MUC4 with erbB2 and the status of erbB2 signalling in human gallbladder carcinomas were determined in order to gain a better understanding of the pathobiology. The expression levels of MUC4 protein and mRNA were increased in specimens of gallbladder carcinoma. Immunoprecipitation experiments showed an interaction between MUC4 and erbB2. This interaction was associated with the hyperphosphorylation of erbB2, MAPK and Akt and with the overexpression of cyclooxygenase-2. MUC4 was detected on the apical surface of cancerous epithelia and partially co-localised there with erbB2. Transfection experiments showed that MUC4 amplifies cell proliferation in the presence of heregulin through potentiating phosphorylation of erbB2 and its downstream signalling pathways. These findings suggest that MUC4 is up-regulated and interacts with erbB2 in human gallbladder carcinoma, and thereby support the potential implication of MUC4 in erbB2 activation.
Miyahara
Naoki
N
Department of Gastroenterology, Institute of Clinical Medicine, University of Tsukuba Graduate School of Comprehensive Human Sciences, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki 305-8575, Japan.
Shoda
Junichi
J
Ishige
Kazunori
K
Kawamoto
Toru
T
Ueda
Tetsuya
T
Taki
Ryuuichi
R
Ohkohchi
Nobuhiro
N
Hyodo
Ichinosuke
I
Thomas
Melanie B
MB
Krishnamurthy
Savitri
S
Carraway
Kermit L
KL
Irimura
Tatsuro
T
D000328:Adult; D000368:Aged; D002450:Cell Communication; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004273:DNA, Neoplasm / Q000378:metabolism; D005260:Female; D005706:Gallbladder Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D055264:Mucin-4; D009077:Mucins / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010766:Phosphorylation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D051546:Cyclooxygenase 2; D004273:DNA, Neoplasm; D020929:Mitogen-Activated Protein Kinase Kinases; D055264:Mucin-4; D009077:Mucins; D051058:Oncogene Protein v-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; C524658:MUC4 protein, human