| Summary: | 碩士 === 台北醫學院 === 細胞及分子生物研究所 === 85 === Esophageal Carcinoma is the tenth most common cancer in the
Taiwanese population and the fifth most common cancer in the
male population of Taiwan. Various genetic abnormalities have
already been reported such as changes of tumor suppressor genes
including p53, APC, MCC that genes are involved in esophageal
carcinoma.The retinoblastoma gene product (pRB) is a nuclear
phosphoprotein that is thought to play a key role in the
negative regulation of cellular proliferation by modulating the
activities of the transcriptional factors that control
expression of S phase genes. D-type cyclins, in association with
the cyclin-dependent kinases Cdk4 or Cdk6, promote progression
through the G1 phase of the cell cycle by phosphorylating the
pRB. The activities of Cdk4 and Cdk6 are constrained by
inhibitors such as p16, the product of the p16 gene on human
chromosome 9p21. The tumor suppressor gene p16(CDKN2/INK4A/MTS1)
has been found to be deleted or mutated in a variety of human
cancers. Thirteen human esophageal carcinoma primary tissue
samples and five human esophageal carcinoma cell lines were
analyzed for Rb gene alteration by single-strand conformational
polymorphism (SSCP), DNA sequence analyses, and western blot
assay. p16 gene alteration were detected by a method combining
reverse transcription and nested polymerase chain reaction to
detect different RNA transcripts of the p16 gene, associate with
western blot assay to detect p16 protein expression, and
polymerase chain reaction-methylation assay to detect the
methylation status of genomic p16 gene in human esophageal
carcinoma.The results showed that 2 of 13 esophageal carcinoma
primary tissue samples and none of 5 esophageal carcinoma cell
lines had altered Rb tumor suppressor gene; 3 of 10 primary
tissue samples didn''t express pRb protein, including 1 primary
tissue sample with altered Rb gene, but all of 5 cell lines
express pRb protein. 8 of 13 primary tissues samples and all of
5 cell lines had altered p16 gene, 4 of 10 primary tissue
samples and all of 5 cell lines fail to express p16 protein.Our
result revealed that inactivation of the p16 tumor suppressor
gene may play an important role in the development of esophageal
carcinoma. But since the Rb tumor suppressor gene transcription
factors binding sites alteration is not a frequent event in
esophageal carcinoma, it will require more studies to understand
Rb''s role in esophageal carcinoma.
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