The long-term goal of this research is to define the role of mucins and altered mucins in the progression of squamous lung carcinoma (SLC). the present application focuses on three questions related to this goal. a) What mucin (MUC) genes coding for mucin core protein are expressed in human SLC cells? b) Do the MUC genes that are being expressed in SLC cells correlate with the aggressiveness of the carcinoma? c) Can changes be detected in the oligosaccharide structure of mucins in sputum specimens of SLC patients and are these changes useful for diagnosis? Total RNA and mRNA will be isolated from a set of cloned human SLC cell lines that differ in aggressiveness of tumor progression when introduced into animal model systems. RNA will also be isolated from a collection of SLC tumor specimens and from normal lung epithelia. Northern blot analyses of the RNA using cDNA probes for the MUC1,2,3 or 4 genes will determine which MUC gene(s) are expressed in the different cell types and it will be possible to correlate the aggressiveness of the different SLC cells or tumors with the active MUC gene(s). In a related project, mucin and epithelial cells obtained from a sputum collection of normal and lung cancer patients will be analyzed to determine the relative contents of the oligosaccharide Lea-X, recognized by monoclonal antibody 43-9F. This subproject will define the diagnostic potential of Lea-X (which was previously shown to be significant in prognosis of SLC) in sputum specimens. Collaborative research is also proposed to augment other projects within the SPORE. These projects will define the expression of cyclins, tyrosine kinases, and cdc kinases in the panel of cloned SLC cell lines and will test the hypothesis that the differing potential for tumor progression of the SLC clones is mediated through the action of one or more of these regulatory proteins.
Showing the most recent 10 out of 435 publications
