Yu Jun, Ohuchida Kenoki, Nakata Kohei, Mizumoto Kazuhiro, Cui Lin, Fujita Hayato, Yamaguchi Hiroshi, Egami Takuya, Kitada Hidehisa, Tanaka Masao
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Mol Cancer. 2008 Dec 22;7:93. doi: 10.1186/1476-4598-7-93.
LIM-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.
We 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).
9 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).
Pancreatic 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.
仅含LIM结构域4（LMO4）是含LIM结构域转录因子的仅含LIM结构域（LMO）亚家族的成员，最初报道其在乳腺癌中具有致癌作用。我们推测LMO4可能与胰腺癌发生有关，就如同其与乳腺癌发生有关一样。如果是这样，这可能有助于更好地理解胰腺癌的肿瘤发生机制。
我们通过定量实时逆转录-聚合酶链反应（qRT-PCR）检测了培养细胞、胰腺大体组织及显微切割的靶细胞（正常导管细胞；胰腺上皮内瘤变-1B[PanIN-1B]细胞；PanIN-2细胞；浸润性导管癌[IDC]细胞；导管内乳头状黏液腺瘤[IPMA]细胞；IPM交界性[IPMB]细胞；以及浸润性和非浸润性IPM癌[IPMC]）中LMO4 mRNA水平。
14种胰腺癌细胞系中有9种表达的LMO4 mRNA水平高于人胰腺导管上皮细胞系（HPDE）。在大体组织样本中，胰腺癌中LMO4的表达高于导管内乳头状黏液性肿瘤（IPMN）或非肿瘤性胰腺（两者均p < 0.0001）。我们进行了基于显微切割的分析。IDC细胞表达的LMO4水平显著高于正常导管上皮或PanIN-1B细胞（两者均p < 0.001）或PanIN-2细胞（p = 0.014）。IPMC细胞表达的LMO4水平显著高于正常导管上皮（p < 0.001）、IPMA（p < 0.001）和IPMB细胞（p = 0.003）。
胰腺癌（IDC和IPMC）表达的LMO4 mRNA水平显著高于正常导管上皮、PanIN-1B、PanIN-2、IPMA和IPMB。这些结果表明LMO4在胰腺癌发生的晚期阶段过度表达。
