Aberrant expression of the gastric mucin MUC6 in human pulmonary adenocarcinoma xenografts.
Certain pulmonary adenocarcinomas show gastrointestinal differentiation with the expression of various mucins. The CDX homeobox gene, an intestine-specific transcription factor, is related to gastric carcinogenesis with MUC2 and MUC6 expression. The intestinal mucin MUC2 is expressed in the normal lung, while the gastric mucin MUC6 is not. Previously, we have reported that the expressions of MUC2 and MUC6 were related to a poor prognosis in small adenocarcinomas of the lung. We estimated the expressions of the mucin (MUC2 and MUC6) and CDX (CDX1 and CDX2) to examine how CDX relates to the gastrointestinal mucin production in the pulmonary adenocarcinoma. Thirty-nine human non-small cell lung cancer (NSCLC) xenografts were examined (13 adenocarcinoma, 18 squamous cell carcinoma and 8 large cell carcinoma). Significant expression of the MUC6 gene was observed in 7 out of 39 (17.9%) NSCLC xenografts. The expressions of the MUC6 genes were noted in 6 out of 13 (46.2%) adenocarcinoma xenografts, but only in 1 of 18 (0.06%) squamous cell carcinoma xenografts. The adenocarcinoma xenografts significantly showed higher expression of the MUC6 gene than squamous cell carcinoma xenografts (t-test, p=0.0343). Four adenocarcinoma-xenografts co-expressed both the MUC2 and MUC6 genes, and the residual 2 adenocarcinoma-xenografts expressed only the MUC6 gene. One MUC6 overexpressing squamous cell carcinoma focally contained an adenocarcinoma component. The expression patterns of the gastrointestinal mucins were analogous to gastric cancer. The cellular morphology of these carcinoma xenografts was of the gastric cancer type. The proteins of the MUC2 and MUC6 were immunohistochemically confirmed in the xenografts. The expression of the MUC6 gene was significantly correlated with the expressions of the CDX1 and CDX2 genes in the xenografts (Fisher's test, p<0.0001 and p=0.0005, respectively), while there was no significant association between the expression of the MUC2 and CDX genes. These results suggest that the expression of CDX molecules in the pulmonary carcinogenesis pathway relates to gastric cancerous features of aberrant MUC6 expression.
Hamamoto
Atsushi
A
Department of General Thoracic Surgery, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan.
Abe
Yoshiyuki
Y
Nishi
Masatake
M
Fujimori
Sakashi
S
Ohnishi
Yasuyuki
Y
Yamazaki
Hitoshi
H
Oida
Yasuhisa
Y
Miyazaki
Noriyuki
N
Inada
Ken-Ichi
K
Ueyama
Yoshito
Y
Iwasaki
Masayuki
M
Inoue
Hiroshi
H
Nakamura
Masato
M
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000818:Animals; D000071616:CDX2 Transcription Factor; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology*; D004064:Digestive System / Q000276:immunology; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D055272:Mucin-6; D009077:Mucins / Q000096:biosynthesis* / Q000235:genetics*; D015534:Trans-Activators / Q000096:biosynthesis; D014183:Transplantation, Heterologous; D015854:Up-Regulation
C491273:CDX1 protein, human; D000071616:CDX2 Transcription Factor; C491272:Cdx1 protein, mouse; D018398:Homeodomain Proteins; C524734:MUC6 protein, human; C524735:Muc6 protein, mouse; D055272:Mucin-6; D009077:Mucins; D015534:Trans-Activators