Characterization of cell-type specific profiles in tissues and isolated cells from squamous cell carcinomas of the lung.
Lung cancer accounts for 28% of all cancer deaths, a higher percentage than any other human cancer. Squamous Cell Carcinoma (SqCC) is the most common lung neoplasm and is a tumor that is extensively associated with tobacco use. Despite the association of many genetic alterations with lung cancer, the precise molecular mechanisms of tumorigenesis, for the most part, remain ambiguous. Although many studies of lung cancer have used global transcript profiling approaches designed to uncover genes or pathways that are important in lung tumorigenesis, no strong candidates have emerged. A lack of concurrence amongst these various studies can be attributed, in a large part, to the cellular heterogeneity within lung tissue. We have attempted to reduce this complication by designing a profiling strategy that will minimize the confounding involvement of tissue heterogeneity in gene expression of lung tumors. Specifically, we have profiled transcript expression levels in both isolated cells and tissues from SqCC and normal samples. Our strategy consists of combining and subtracting the input of these various cell types which has produced a unique transcript profile of the squamous carcinoma cell. We then analyzed the data using Pathways Assist analysis software to determine which processes may be involved in SqCC tumorigenesis. The MAP/ERK pathway involved in growth and differentiation was the pathway that was most frequently identified across all comparisons. In addition, biological interaction networks of the SqCC profile identified IL-8 as playing a potentially important role SqCC development.
Hawthorn
Lesleyann
L
Department of Cancer Genetics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14163, United States. Lesleyann.Hawthorn@RoswellPark.org
Stein
Leighton
L
Panzarella
Jenniffer
J
Loewen
Gregory M
GM
Baumann
Heinz
H
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D016209:Interleukin-8; D048049:Extracellular Signal-Regulated MAP Kinases