DISCOVERY OF NEW SECRETED PROTEINS OF PANCREATIC CANCER

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The identification of serum tumor markers can markedly enhance the ability for early diagnosis, efficient assessment of treatment and early discovery of recurrence of cancers. This potential has been most elegantly shown through the discovery of prostate-specific antigen (PSA) which has markedly advanced screening and monitoring of prostate cancer. We have developed an approach to isolate new serum tumor markers of cancer. We propose using molecular biology techniques in order to screen for secreted proteins of tumors that can be used as markers for early detection of cancer. Identification of one or several markers of pancreatic cancer could have profound implications for the management of this disease. If we are successful, the serum markers will provide the first opportunity for a simple, rapid, inexpensive method of screening for pancreatic cancer. Monitoring and management of the disease during therapy would be markedly enhanced and early recurrence could be rapidly detected when tumor burden is low. Specific Aim 1: Confirmation of preliminary experiments using a modification of the signal sequence trap technique, utilizing the SUC2 gene encoding a secreted protein of yeast. In this system only the yeast which have been transformed with cDNAs containing secretory signal sequences can grow into colonies on the plates which contain sucrose as the only source of sugar. Specific Aim 2: We will construct a human pancreatic cancer cDNA library which has been enriched for pancreatic-specific genes, and this library will be placed in our yeast based signal sequence trap vector in order to identify genes encoding secreted proteins. Specific Aim 3: After identifying candidate cDNAs, we will further select for novel pancreatic-specific genes by dot blotting and DNA sequencing, and we will clone full-length cDNAs to make antibodies against the gene products. Specific Aim 4: For antibodies that appear to be pancreatic-specific (and ideally, pancreatic cancer-selective protein), an ELISA will be developed to examine for the presence of the pancreatic-specific, secreted protein in serum samples from pancreatic cancer patients as well as normal individuals.