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ROLE OF HSAL 2 IN OVARIAN CANCER

Award Number: K08CA097185
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 08/01/2003
PERIOD OF PERFORMANCE END DATE: 07/31/2008

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ROLE OF HSAL 2 IN OVARIAN CANCER - DESCRIPTION (provided by applicant): Dr. Ma's overall goal is to acquire the skills and knowledge to pursue research in the field of human cancer biology and become an independent physician-scientist in this field, which is a considerable departure from his prior experience. Pursuing the outlined practical and didactic training and other mentored activities will be key toward achieving this end. The overall research goal is to elucidate the role of the homeobox gene Hsal 2 in ovarian cancer initiation and development. Determining the underlying mechanisms of this very aggressive cancer is critical for developing new therapies and improving survival. The PI's prior research demonstrated a new tumor suppressor gene, Hsal 2, homologous to the Sal homeobox gene in Drosophila, that is altered or missing in most ovarian epithelial cancer cells. Re-expression of this gene inhibits growth and DNA synthesis of an ovarian cancer cell line and inhibits tumor formation in nude mice. The PI has also demonstrated that the transcriptional regulation of Hsal 2 is controlled by two independent promoters and that Hsal 2 promoter usage is altered in some human cancers. In mice, Hsal 2 is able to bind to the large T antigen of polyoma virus, a virus that induces a broad variety of neoplasms. His studies provide strong evidence that Hsal 2 may be a potential tumor suppressor gene for ovarian cancer. These and other observations led to the hypothesis that Hsal 2 isoforms may play a role in the initiation and development of ovarian cancer. To test this, two specific aims will examine the functional roles and underlying mechanisms of expression of Hsal 2 isoforms. Aim 1 will determine the role of altered Hsal 2 isoform expression in ovarian cancer initiation and progression by studying the effect of Hsal 2 isoform overexpression on tumorigenicity, identifying target genes that are subordinate to Hsal 2 isoform expression, and characterizing upstream regulators of Hsal 2 isoforms. Aim 2 will determine the underlying mechanism of altered Hsal 2 isoform expression in ovarian cancer by delineating the usage of Hsal 2 P1 and P2 promoters and measuring the methylation status of CpG islands in Hsal 2 isoform promoters and correlating this with their expression in ovarian cancer. These studies will provide insight into the mechanism(s) of Hsal 2 in controlling growth and differentiation of ovarian normal epithelial cells. If down-regulation of Hsal 2 is shown to activate certain oncogenic pathways or repress tumor suppressor gene pathway(s) in ovarian cancer cells, therapeutic drugs that specifically target these pathways could be designed.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2007 ( Subtotal = $133,650 )
2007	2007	Nevada Cancer Institute	STE 260	IAS VEGAS	NV	89135		USA	Cancer Research Manpower	000	5	7/20/2007	NON-COMPETING CONTINUATION	$133,650
														Subtotal = $133,650

Issue Date FY: 2006 ( Subtotal = $133,650 )
2006	2006	Nevada Cancer Institute	STE 260	IAS VEGAS	NV	89135		USA	Cancer Research Manpower	000	4	8/4/2006	NON-COMPETING CONTINUATION	$133,650
														Subtotal = $133,650

Issue Date FY: 2005 ( Subtotal = $133,650 )
2005	2005	Nevada Cancer Institute	STE 260	IAS VEGAS	NV	89135		USA	Cancer Research Manpower	000	3	9/13/2005	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$133,650
														Subtotal = $133,650

Issue Date FY: 2004 ( Subtotal = $133,650 )
2004	2004	UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES	4301 W MARKHAM ST, M S 545	LITTLE ROCK	AR	72205	PULASKI	USA	Cancer Research Manpower	000	2	7/16/2004	NON-COMPETING CONTINUATION	$133,650
														Subtotal = $133,650

Issue Date FY: 2003 ( Subtotal = $133,650 )
2003	2003	UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES	4301 W MARKHAM ST, M S 545	LITTLE ROCK	AR	72205	PULASKI	USA	Cancer Research Manpower	000	1	8/1/2003	NEW	$133,650
														Subtotal = $133,650

Grand Total All Awards = $668,250

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ROLE OF HSAL 2 IN OVARIAN CANCER

Award Number: K08CA097185

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 08/01/2003

PERIOD OF PERFORMANCE END DATE: 07/31/2008

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