Abstract

This is the first submission of an RO1 application to examine the function and regulation of the gastrointestinal hormone gastrin. This peptide hormone is important as a gastric secretagogue in addition to promoting mucosal growth. There have been recent intriguing studies suggesting that the precursor forms of this peptide hormone may be involved in regulating cell proliferation and perhaps even be involved in the development of colorectal carcinoma. The overall objective of this proposal is to study the tissue specific regulation and function of gastrin in the colonic mucosa and stomach using transgenic and knockout mice. The three specific aims are: a) Determine the cis-acting DNA sequences required for colonic specific expression with a mouse gastrin gene. b) Elucidate whether over-expression of incompletely processed forms of gastrin stimulate colonic proliferation and predispose mice to colonic carcinoma. c) Evaluate the role of gastrin in gastrointestinal tract development.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK052778-04
Application #
6178165
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
May, Michael K
Project Start
1997-09-01
Project End
2000-08-31
Budget Start
2000-07-01
Budget End
2000-08-31
Support Year
4
Fiscal Year
2000
Total Cost
$152,582
Indirect Cost

  Institution

Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199

  Publications

Hayakawa, Yoku; Fox, James G; Wang, Timothy C (2017) Isthmus Stem Cells Are the Origins of Metaplasia in the Gastric Corpus. Cell Mol Gastroenterol Hepatol 4:89-94
Hayakawa, Yoku; Fox, James G; Wang, Timothy C (2017) The Origins of Gastric Cancer From Gastric Stem Cells: Lessons From Mouse Models. Cell Mol Gastroenterol Hepatol 3:331-338
Hayakawa, Yoku; Sakitani, Kosuke; Konishi, Mitsuru et al. (2017) Nerve Growth Factor Promotes Gastric Tumorigenesis through Aberrant Cholinergic Signaling. Cancer Cell 31:21-34
Sakitani, Kosuke; Hayakawa, Yoku; Deng, Huan et al. (2017) CXCR4-expressing Mist1+ progenitors in the gastric antrum contribute to gastric cancer development. Oncotarget 8:111012-111025
Hayakawa, Yoku; Ariyama, Hiroshi; Stancikova, Jitka et al. (2015) Mist1 Expressing Gastric Stem Cells Maintain the Normal and Neoplastic Gastric Epithelium and Are Supported by a Perivascular Stem Cell Niche. Cancer Cell 28:800-814
Hayakawa, Yoku; Jin, Guangchun; Wang, Hongshan et al. (2015) CCK2R identifies and regulates gastric antral stem cell states and carcinogenesis. Gut 64:544-53
Ramanathan, Vigneshwaran; Jin, Guangchun; Westphalen, Christoph Benedikt et al. (2012) P53 gene mutation increases progastrin dependent colonic proliferation and colon cancer formation in mice. Cancer Invest 30:275-86
Takaishi, Shigeo; Shibata, Wataru; Tomita, Hiroyuki et al. (2011) In vivo analysis of mouse gastrin gene regulation in enhanced GFP-BAC transgenic mice. Am J Physiol Gastrointest Liver Physiol 300:G334-44
Yang, Xiang Dong; Ai, Walden; Asfaha, Samuel et al. (2011) Histamine deficiency promotes inflammation-associated carcinogenesis through reduced myeloid maturation and accumulation of CD11b+Ly6G+ immature myeloid cells. Nat Med 17:87-95
Wang, Judy S; Varro, Andrea; Lightdale, Charles J et al. (2010) Elevated serum gastrin is associated with a history of advanced neoplasia in Barrett's esophagus. Am J Gastroenterol 105:1039-45

Showing the most recent 10 out of 24 publications