Pancreatic Cancer Genes
The present invention provides the art with the DNA coding sequences of polynucleotides that are up-or-down-regulated in cancer and dysplasia. These polynucleotides and encoded proteins or polypeptides can be used in the diagnosis or identification of cancer and dysplasia. Inhibitors of the up-regulated polynucleotides and proteins can decrease the abnormality of cancer and dysplasia. Enhancing the expression of down-regulated polynucleotides or introducing down-regulated proteins to cells can decrease the growth and/or abnormal characteristics of cancer and dysplasia.
1 . An isolated subgenomic polynucleotide comprising at least twelve contiguous nucleotides of SEQ ID NO:12, or the full complement of said at least twelve contiguous nucleotides of SEQ ID NO:12.
2 . The isolated subgenomic polynucleotide of claim 1 comprising at least eighteen contiguous nucleotides of SEQ ID NO: 12.
3 . The isolated subgenomic polynucleotide of claim 1 , wherein said polynucleotide is a nucleotide probe comprising at least twenty-five contiguous nucleotides of SEQ ID NO:12, or the full complement of said at least twenty-five contiguous nucleotides of SEQ ID NO:12.
4 . The isolated subgenomic polynucleotide of claim 3 , wherein said probe comprises at least fifty contiguous nucleotides of SEQ ID NO:12.
5 . The isolated subgenomic polynucleotide of claim 1 , wherein said polynucleotide comprises a polynucleotide sequence selected from the group consisting of: (a) the polynucleotide sequence of SEQ ID NO:12; and (b) a polynucleotide sequence fully complementary to (a).
6 . The isolated subgenomic polynucleotide of claim 1 , wherein said polynucleotide comprises: (a) a SEQ ID NO:12 or a naturally occurring variant of SEQ ID NO:12, wherein said naturally occurring variant hybridizes to SEQ ID NO:12 under conditions including a wash in 2×SCC, 0.1% SDS at 50° C. for 20 minutes, wherein the nucleotide sequence encodes a polypeptide underexpressed in cancer, or (b) the full complement of the nucleotide sequence of (a).
7 . The isolated subgenomic polynucleotide of claim 6 , wherein the polypeptide is underexpressed in pancreatic cancer cells.
8 . A composition comprising an amount of a polynucleotide comprising SEQ ID NO:12 or a naturally occurring variant of SEQ ID NO:12, wherein said naturally occurring variant hybridizes to SEQ ID NO:12 under conditions including a wash in 2×SCC, 0.1% SDS at 50° C. for 20 minutes, wherein said polynucleotide is operably linked to a promoter sequence; and a pharmaceutically acceptable carrier, said amount effective to reduce the growth rate of contacted cancer cells by at least 50% as compared to a control.
9 . A method of diagnosing cancer in a patient comprising comparing the amount of mRNA molecules in a patient sample and in a normal sample, wherein said mRNA molecules are complementary to a polynucleotide sequence comprising at least twelve contiguous nucleotides of SEQ ID NO:12, or the full complement of said at least twelve contiguous nucleotides of SEQ ID NO:12; and wherein a patient sample containing less of said mRNA molecules than the normal sample is identified as cancerous.
10 . The method of claim 9 , wherein said mRNA molecules are complementary to the polynucleotide sequence of SEQ ID NO:12, or a naturally occurring variant of SEQ ID NO:12, wherein said naturally occurring variant hybridizes to SEQ ID NO:12 under conditions including a wash in 2×SCC, 0.1% SDS at 50° C. for 20 minutes, or the complement of SEQ ID NO:12 or said naturally occurring variant of SEQ ID NO:12.
11 . The method of claim 10 wherein the cancer is pancreatic cancer.
12 . A method of diagnosing cancer in a patient comprising determining the amount of a first mRNA molecule in a patient sample and in a normal sample, wherein said first mRNA molecule is complementary to the minus strand of a double-stranded polynucleotide sequence, wherein said double-stranded polynucleotide has the sequence is selected from the group of polynucleotides as shown in SEQ ID NOS:1, 3-4, 6-11, and 13-14; determining the amount of a second mRNA molecule in the patient sample and in the normal sample, wherein said second mRNA molecule is complementary to the minus strand of a double-stranded sequence, wherein said double-stranded polynucleotide sequence is SEQ ID NO: 12; and comparing the determined amounts; wherein a patient sample which contains less of the second mRNA molecule than the normal sample and which contains substantially the same amount of the first mRNA molecule, as compared to the normal sample, is identified as cancerous.
14 . The method of any one of claim 9 , 10 , or 13 wherein the patient sample and the normal sample comprise pancreatic cells.
15 . A method for treating cancer in a patient having said cancer, said method comprising administering to said patient a composition comprising: an amount of a polynucleotide comprising SEQ ID NO:12 or a naturally occurring variant of SEQ ID NO:12, wherein said naturally occurring variant hybridizes to SEQ ID NO:12 under conditions including a wash in 2×SCC, 0.1% SDS at 50° C. for 20 minutes, wherein said polynucleotide is operably linked to a promoter sequence; and a pharmaceutically acceptable carrier, said amount effective to reduce the growth rate of contacted pancreatic cancer cells by at least 50% as compared to a control.
16 . The method of claim 15 , wherein said polynucleotide sequence encodes a polypeptide encoded for by SEQ ID NO:12.