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The aim of the present study was to evaluate the effects of the REG Iα and REG Iβ genes on lung cancer cell lines, and thereafter, the expression of REG family genes (REG Iα, REG Iβ, REG III, HIP/PAP and REG IV) in lung cancer in relation to patient prognosis was evaluated. Lung adenocarcinoma (AD) and squamous cell carcinoma (SCC) cell lines expressing REG Iα or REG Iβ (HLC-1 REG Iα/Iβ and EBC-1 REG Iα/Iβ) were established, and cell number, cell invasive activity, and anchorage-independent cell growth were compared with these variables in the control cells. The expression levels of REG family genes were evaluated by real-time RT-PCR in surgically resected lung cancers, and disease-specific survival (DSS) curves were generated. The HLC-1 REG Iα/Iβ cell line showed significant increases in cell number and anchorage-independent cell growth compared with the control cells. EBC-1 REG Iα/Iβ cells showed significant increases in cell invasive activity and anchorage-independent cell growth as compared with the control cells. Except for the REG Iβ gene, expression of other REG family genes was observed in the surgically resected samples; however, DSS was significantly worse only in stage I patients who were positive for REG Iα expression than in patients who were negative for REG Iα expression. The effects of REG Iα on AD and SCC cells were different in the in vitro study, and a correlation between REG Iα expression and patient prognosis was noted in the in vivo study. Therefore, overexpression of REG Iα is a risk factor for poor prognosis caused by discrete mechanisms in AD and SCC patients.

Pancreatic regenerating gene (reg I) messenger RNA is overexpressed within the pancreas following injury and resection. Its level of expression corresponds to the level of cellular dedifferentiation. Human reg I has been localized to chromosome 2p12, and ectopic expression of its mRNA has been found within colorectal tumors. We postulated that colorectal production of reg I might either be a marker for the presence of cancer or define mucosa at risk for development of neoplasia. Using a monoclonal antibody to reg I, regenerating gene protein was histochemically mapped in 56 cases of documented colorectal adenocarcinoma. In sections of colon from normal control subjects no reg I protein was noted, whereas 58.9% of the specimens from cancer patients stained positive for reg I. Although a correlation was noted between reg I staining and Dukes' stage, there was no correlation with histologic grade or 5-year patient survival. In 39 of 55 cancer specimens the transition zone (interface) between the neoplasm and normal mucosa was visualized; 100% of the transition zones contained cells that stained strongly positive for reg I. We conclude that reg I protein is ectopically expressed in colorectal mucosa at the transition zone of colorectal cancer, and occasionally within the tumor itself. Although ectopic reg I expression in colorectal epithelia is not a marker for the presence of carcinoma, it may be a sensitive marker for mucosa at risk for development of neoplasia.