Induction and expression of cyclin D3 in human pancreatic cancer.
OBJECTIVE
Cyclins play a key role in the control and regulation of the cell cycle. The role of cyclins in the pathogenesis of pancreatic cancer is largely unknown.


METHODS
Using Northern blot analysis, polymerase chain reaction (PCR) and immunohistochemistry, we examined the expression of cyclins D1, D2, and D3 in human pancreatic cancer and studied the induction of these cyclins by growth factors in pancreatic cancer cell lines.


RESULTS
We now report that cyclin D1 and D3 mRNAs are expressed in human pancreatic cancer cell lines, and that the expression of cyclin D3 is enhanced in pancreatic cancer cells by amphiregulin, a member of the epidermal growth factor family. Cyclins D1 and D3 are also expressed in normal and malignant pancreatic tissues. However, while the normal pancreas and pancreatic cancers express cyclin D2 as determined by reverse-transcriptase PCR, we could not detect cyclin D2 mRNA by either Northern blot analysis or reverse transcriptase PCR in the two pancreatic cancer cell lines. Immunohistochemical analysis revealed the expression of cyclin D3 in pancreatic cancer cells.


CONCLUSIONS
These findings suggest that D-type cyclins are differentially expressed in pancreatic cancer and that the aberrant activation of the EGF receptor in human pancreatic cancer by amphiregulin may lead to the progression of the cell cycle via induction of cyclin D3 expression, thus contributing to the growth advantage of these transformed cells.
Ebert
M P
MP
Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University of Magdeburg, Germany. Matthias.Ebert@medizin.uni-magdeburg.de
Hernberg
S
S
Fei
G
G
Sokolowski
A
A
Schulz
H U
HU
Lippert
H
H
Malfertheiner
P
P
D066258:Amphiregulin; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D056743:Cyclin D3; D016213:Cyclins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D066255:EGF Family of Proteins; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006023:Glycoproteins / Q000378:metabolism* / Q000494:pharmacology; D006133:Growth Substances / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
C587848:AREG protein, human; D066258:Amphiregulin; D000970:Antineoplastic Agents; C534696:CCND3 protein, human; D056743:Cyclin D3; D016213:Cyclins; D066255:EGF Family of Proteins; D006023:Glycoproteins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger