Immunohistochemical analysis of apoptosis-related proteins in human embryonic and fetal pancreatic tissues.
BACKGROUND
The growth of both cancer cells and fetal tissue is rapid; however, cancer cells de-differentiate and proliferate in a disorderly manner, whereas fetal tissues differentiate and proliferate in an orderly manner. Thus, there may be both common and different factors that are involved in the process of the uncontrolled cell growth of pancreatic cancers and the development of the fetal pancreas. The common part of the mechanisms should be in the regulation of the cell cycle, resulting in rapid proliferation via such mechanisms as growth stimulation and avoidance of apoptosis. Therefore, in the current study we investigated the expression of apoptosis-related proteins in fetal pancreatic tissues.


METHODS
Sixteen human embryonic and fetal pancreatic tissues obtained between 6 and 32 wk of gestation were used. We immunohistochemically examined the protein expression of Bcl-2, Bcl-XL, Mcl-1, and Bax. Further, the expression of insulin, glucagon, and proliferting cell nuclear antigen (PCNA), and TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining were examined.


RESULTS
In embryonic and fetal pancreatic tissues, Bcl-2 was not detected in any type of pancreatic cell (acinar, ductal, or islet). Bcl-XL was expressed in all types of pancreatic cells throughout the gestation. Mcl-1 was expressed in all types of pancreatic components, and strongly expressed in the margin of the islets. Bax, a pro-apoptotic protein, was expressed in all components. PCNA was strongly expressed in the embryonic and fetal pancreas, especially in early stages of gestation; however, TUNEL staining was negative in all samples. At least one antiapoptotic protein was expressed in all types of pancreatic cells.


CONCLUSIONS
The results of the current study indicate that active proliferation and avoidance of apoptosis take place in embryonic and fetal pancreatic tissues, which may be controlled by particular combinations of apoptosis-related proteins. Among these proteins, Bcl-XL and Mcl-1 may play an important role in the proliferation and differentiation of the embryonic and fetal pancreas.
Kobayash
H
H
Department of Surgery and Surgical Basic Science, Kyoto University, Sakyo, Japan. khiro@kuhp.kyoto-u.ac.jp
Doi
R
R
Hosotani
R
R
Miyamoto
Y
Y
Koshiba
T
T
Fujimoto
K
K
Ida
J
J
Tsuji
S
S
Nakajima
S
S
Kawaguchi
M
M
Shiota
K
K
Imamura
M
M
D017209:Apoptosis / Q000502:physiology*; D005314:Embryonic and Fetal Development; D005333:Fetus / Q000378:metabolism* / Q000502:physiology; D005934:Glucagon / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007328:Insulin / Q000378:metabolism; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000378:metabolism; D010179:Pancreas / Q000196:embryology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013194:Staining and Labeling; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494826:BAX protein, human; C494811:BCL2L1 protein, human; D007328:Insulin; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D018809:Proliferating Cell Nuclear Antigen; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D005934:Glucagon