Abstract
BackgroundLIM-only 4 (LMO4), a member of the LIM-only (LMO) subfamily of LIM domain-containing transcription factors, was initially reported to have an oncogenic role in breast cancer. We hypothesized that LMO4 may be related to pancreatic carcinogenesis as it is in breast carcinogenesis. If so, this could result in a better understanding of tumorigenesis in pancreatic cancer.MethodsWe measured LMO4 mRNA levels in cultured cells, pancreatic bulk tissues and microdissected target cells (normal ductal cells; pancreatic intraepithelial neoplasia-1B [PanIN-1B] cells; PanIN-2 cells; invasive ductal carcinoma [IDC] cells; intraductal papillary-mucinous adenoma [IPMA] cells; IPM borderline [IPMB] cells; and invasive and non-invasive IPM carcinoma [IPMC]) by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR).Results9 of 14 pancreatic cancer cell lines expressed higher levels of LMO4 mRNA than did the human pancreatic ductal epithelial cell line (HPDE). In bulk tissue samples, expression of LMO4 was higher in pancreatic carcinoma than in intraductal papillary-mucinous neoplasm (IPMN) or non-neoplastic pancreas (p < 0.0001 for both). We carried out microdissection-based analyses. IDC cells expressed significantly higher levels of LMO4 than did normal ductal epithelia or PanIN-1B cells (p < 0.001 for both) or PanIN-2 cells (p = 0.014). IPMC cells expressed significantly higher levels of LMO4 than did normal ductal epithelia (p < 0.001), IPMA (p < 0.001) and IPMB cells (p = 0.003).ConclusionPancreatic carcinomas (both IDC and IPMC) expressed significantly higher levels of LMO4 mRNA than did normal ductal epithelia, PanIN-1B, PanIN-2, IPMA and IPMB. These results suggested that LMO4 is overexpressed at late stages in carcinogenesis of pancreatic cancer.
Highlights
Pancreatic cancer is one of the most aggressive malignant tumors
Quantitative analysis of LIM-only 4 (LMO4) expression in 14 pancreatic cancer cell lines, a non-neoplastic ductal epithelial cell line and six primary cultures of pancreatic fibroblasts We investigated LMO4 mRNA expression in 14 pancreatic cancer cell lines, human pancreatic ductal epithelial cell line (HPDE), a normal pancreatic ductal cell line immortalized by transduction with the E6/E7 genes of human papillomavirus 16 [29,30], and 6 primary cultures of pancreatic fibroblasts derived from resected pancreatic tumors
We found that all 6 primary cultures of pancreatic fibroblasts expressed moderate levels of LMO4
Summary
Pancreatic cancer is one of the most aggressive malignant tumors. It is the fifth leading cause of cancer death in Japan [1,2] and has the lowest survival rate of any solid cancer [3]. Because the lack of specific symptoms in patients with pancreatic cancer makes early diagnosis difficult, initial diagnosis typically occurs when the tumor has reached an advanced stage [4]. We hypothesized that LMO4 may be related to pancreatic carcinogenesis as it is in breast carcinogenesis. If so, this could result in a better understanding of tumorigenesis in pancreatic cancer
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