PATHOGENESIS OF HUMAN PROSTATE CARCINOMAS
PATHOGENESIS OF HUMAN PROSTATE CARCINOMAS
批准号:
6172525
负责人:
PRADIP ROY-BURMAN
金额:
$46.86万
依托单位国家:
美国
项目类别:
财政年份:
1993
资助国家:
美国
项目状态:
已结题
起止时间:
1993-06-01 至 2003-04-30
关键词:
adenocarcinoma antisense nucleic acid athymic mouse epithelium fibroblast growth factor gene frequency gene mutation growth factor receptors histopathology human tissue in situ hybridization metastasis molecular oncology natural gene amplification neoplasm /cancer genetics neoplastic cell neoplastic process oncoproteins p53 gene /protein polymerase chain reaction prostate neoplasms protein isoforms stress proteins transcription factor transfection tumor suppressor genes
中文摘要
该计划的长期目标是确定多个分子
在人类前列腺癌的发病机制中相互作用的事件。 我们
获得的证据表明,
前列腺癌的基因雄激素亚型的分子克隆-
诱导生长因子或FGF 8,在人前列腺癌细胞中表达,
进行了分离和表征。 对它们的功能研究
表明FGF 8表达有助于细胞的生物学行为,
前列腺癌细胞 在前列腺恶性上皮中我们发现
另外两个有趣的基因的过度表达:HSF 1,热休克,
因子和L-纤维蛋白酶,肌动蛋白捆绑蛋白亚型。 核
转录因子HSF 1似乎主要定位于
低风险(B期)前列腺癌细胞的细胞质,而其
在高危(C期)前列腺的核中分布增加
癌细胞 抑制L-质体蛋白表达导致抑制
前列腺癌细胞的运动和侵袭。 我们建议扩大
这些研究旨在确定FGF 8同种型和
FGF受体家族成员在基质和上皮细胞中表达,
前列腺细胞,以及这些相互作用在前列腺中的作用
癌症进展 HSF 1过表达的基础和潜力
将研究其亚细胞定位的新方面。
关于L-plastin,我们将具体检查前列腺癌是否
高效、组织工程化的抗肿瘤药物能有效地抑制肿瘤的侵袭和转移,
特异性反义L-plastin基因表达。 来扩展我们的小说
发现腺内和瘤内的频繁发生
前列腺肿瘤中p53突变的遗传异质性,我们还将
试图确定p53突变是否会拯救缺氧的前列腺
癌细胞或来自具有p53突变的病灶区域的细胞是否具有
更容易转移 这些研究结合起来,
应该会对前列腺癌的发病机制有新的认识。
最终,对这些分子事件的理解将为我们提供
新的方法来治疗和/或管理这一问题,
越来越常见的疾病。
英文摘要
The long-term goal of this program is to identify multiple molecular
events that interplay in the pathogenesis of human prostate cancer. We
obtained evidence for the association of abnormal expression of several
genes in prostate cancer. Molecular clones of isoforms of androgen-
induced growth factor or FGF8, expressed in human prostate cancer cells,
were isolated and characterized. Functional studies with them have
suggested that FGF8 expression contributes to biological behavior of
prostate cancer cells. In the prostatic malignant epithelium we found
overexpression of two other interesting genes: HSF1, a heat shock
factor, and L-plastin, an actin-bundling protein isoform. The nuclear
transcription factor HSF1 appears to be primarily localized in the
cytoplasm of the low risk (stage B) prostate carcinoma cells, while its
distribution is increased in the nucleus of high risk (stage C) prostate
cancer cells. Inhibition of L-plastin expression results in suppression
of motility and invasion of prostate cancer cells. We propose to extend
these studies to determine the interactions between FGF8 isoforms and
members of the FGF receptor family expressed in stromal and epithelial
cells of the prostate, and the role of these interactions in prostate
cancer progression. The basis of HSF1 overexpression and potential
novel aspects of its subcellular localization will be investigated.
Concerning L-plastin, we will specifically examine if prostate cancer
invasion and metastasis can be inhibited by high efficiency, tissue
specific antisense L-plastin gene expression. To extend our novel
finding of the frequent occurrence of intraglandular and intratumor
genetic heterogeneity of p53 mutations in prostate tumors, we will also
seek to determine if p53 mutations arise to rescue hypoxic prostate
cancer cells or whether cells from focal regions with p53 mutations have
a higher propensity to metastasize. These studies, in combination,
should lead to new insights into the pathogenesis of prostate cancer.
Ultimately, an understanding of these molecular events will provide us
with new approaches to the treatment and/or management of this
increasingly common disease.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Bone matrix proteins in prostate cancer progression
-
批准号:6899971
-
项目类别:
-
资助金额:$32.09万
-
财政年份:2005
-
负责人:PRADIP ROY-BURMAN
-
依托单位:
Bone matrix proteins in prostate cancer progression
-
批准号:7086405
-
项目类别:
-
资助金额:$31.42万
-
财政年份:2005
-
负责人:PRADIP ROY-BURMAN
-
依托单位:
Bone matrix proteins in prostate cancer progression
-
批准号:8065265
-
项目类别:
-
资助金额:$3.24万
-
财政年份:2005
-
负责人:PRADIP ROY-BURMAN
-
依托单位:
Bone matrix proteins in prostate cancer progression
-
批准号:7393287
-
项目类别:
-
资助金额:$30.52万
-
财政年份:2005
-
负责人:PRADIP ROY-BURMAN
-
依托单位:
Bone matrix proteins in prostate cancer progression
-
批准号:7212265
-
项目类别:
-
资助金额:$30.52万
-
财政年份:2005
-
负责人:PRADIP ROY-BURMAN
-
依托单位:
Bone matrix proteins in prostate cancer progression
-
批准号:7609072
-
项目类别:
-
资助金额:$30.52万
-
财政年份:2005
-
负责人:PRADIP ROY-BURMAN
-
依托单位:
PATHOGENESIS OF HUMAN PROSTATE CARCINOMAS
-
批准号:6375988
-
项目类别:
-
资助金额:$47.44万
-
财政年份:1993
-
负责人:PRADIP ROY-BURMAN
-
依托单位:
PATHOGENETIC MECHANISMS IN FELINE LEUKEMIA
-
批准号:2094298
-
项目类别:
-
资助金额:$3.4万
-
财政年份:1993
-
负责人:PRADIP ROY-BURMAN
-
依托单位:
PATHOGENESIS OF HUMAN PROSTATE CARCINOMAS
-
批准号:2696921
-
项目类别:
-
资助金额:$40.72万
-
财政年份:1993
-
负责人:PRADIP ROY-BURMAN
-
依托单位:
PATHOGENESIS AND PROGRESSION OF PROSTATE CANCER
-
批准号:8244675
-
项目类别:
-
资助金额:$5.91万
-
财政年份:1993
-
负责人:PRADIP ROY-BURMAN
-
依托单位:
PATHOGENESIS AND PROGRESSION OF PROSTATE CANCER
-
批准号:7934239
-
项目类别:
-
资助金额:$5.98万
-
财政年份:1993
-
负责人:PRADIP ROY-BURMAN
-
依托单位:
PATHOGENESIS OF HUMAN PROSTATE CARCINOMAS
-
批准号:2390776
-
项目类别:
-
资助金额:$32.57万
-
财政年份:1993
-
负责人:PRADIP ROY-BURMAN
-
依托单位:
PATHOGENESIS OF HUMAN PROSTATE CARCINOMAS
-
批准号:2100285
-
项目类别:
-
资助金额:$29.57万
-
财政年份:1993
-
负责人:PRADIP ROY-BURMAN
-
依托单位:
PATHOGENESIS OF HUMAN PROSTATE CARCINOMAS
-
批准号:2100286
-
项目类别:
-
资助金额:$30.87万
-
财政年份:1993
-
负责人:PRADIP ROY-BURMAN
-
依托单位:
PATHOGENESIS AND PROGRESSION OF PROSTATE CANCER
-
批准号:7526346
-
项目类别:
-
资助金额:$56.99万
-
财政年份:1993
-
负责人:PRADIP ROY-BURMAN
-
依托单位:
Pathogenesis of human prostate carcinomas
-
批准号:7228189
-
项目类别:
-
资助金额:$54.29万
-
财政年份:1993
-
负责人:PRADIP ROY-BURMAN
-
依托单位:
PATHOGENESIS AND PROGRESSION OF PROSTATE CANCER
-
批准号:7663241
-
项目类别:
-
资助金额:$56.91万
-
财政年份:1993
-
负责人:PRADIP ROY-BURMAN
-
依托单位:
PATHOGENESIS OF HUMAN PROSTATE CARCINOMAS
-
批准号:2100284
-
项目类别:
-
资助金额:$27.75万
-
财政年份:1993
-
负责人:PRADIP ROY-BURMAN
-
依托单位:
PATHOGENESIS OF HUMAN PROSTATE CARCINOMAS
-
批准号:6313444
-
项目类别:
-
资助金额:$3.16万
-
财政年份:1993
-
负责人:PRADIP ROY-BURMAN
-
依托单位:
Pathogenesis of human prostate carcinomas
-
批准号:6919951
-
项目类别:
-
资助金额:$54.16万
-
财政年份:1993
-
负责人:PRADIP ROY-BURMAN
-
依托单位:
海外基金