Htra3 is downregulated in cancer cell lines and significantly reduced in primary serous and granulosa cell ovarian tumors

Harmeet Singh, Ying Li, Peter J. Fuller, Craig Harrison, Jyothsna Rao, Andrew N. Stephens, Gui-Ying Nie

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Objective. The high temperature requirement factor A3 (HtrA3) is a serine protease homolo-gous to bacterial HtrA. Four human HtrAs have been identified. HtrA1 and HtrA3 share a high degree of domain organization and are downregulated in a number of cancers, suggesting a widespread loss of these proteases in cancer. This study examined how extensively the HtrA (HtrA1-3) proteins are downregulated in commonly used cancer cell lines and primary ovarian tumors. Methods. RT-PCR was applied to various cancer cell lines (n=17) derived from the ovary, en-dometrium, testes, breast, prostate, and colon, and different subtypes of primary ovarian tumors [granulosa cell tumors (n=19), mucinous cystadenocarcinomas (n=6), serous cystadenocarcino-mas (n=8)] and normal ovary (n = 9). HtrA3 protein was localized by immunohistochemistry. Results. HtrA3 was extensively downregulated in the cancer cell lines examined including the granulosa cell tumor-derived cell lines. In primary ovarian tumors, the HtrA3 was significantly lower in serous cystadenocarcinoma and granulosa cell tumors. In contrast, HtrA1 and HtrA2 were expressed in all samples with no significant differences between the control and tumors. In normal postmenopausal ovary, HtrA3 protein was localized to lutenizing stromal cells and corpus albicans. In serous cystadenocarcinoma, HtrA3 protein was absent in the papillae but detected in the mesenchymal cyst wall. Conclusion. HtrA3 is more extensively downregulated than HtrA1-2 in cancer cell lines. HtrA3, but not HtrA1 or HtrA2, was decreased in primary ovarian serous cystadenocarcinoma and granulosa cell tumors. This study provides evidence that HtrA3 may be the most relevant HtrA associated with ovarian malignancy.
Original languageEnglish
Pages (from-to)152-164
Number of pages13
JournalJournal of Cancer
Volume4
Issue number2
DOIs
Publication statusPublished - 2013
Externally publishedYes

Keywords

  • GCT
  • HtrA3
  • Ovarian cancer
  • Protease
  • Serous cystadenocarcinoma

Cite this

@article{7800f4bdbd5d4d3bb094efc92671c869,
title = "Htra3 is downregulated in cancer cell lines and significantly reduced in primary serous and granulosa cell ovarian tumors",
abstract = "Objective. The high temperature requirement factor A3 (HtrA3) is a serine protease homolo-gous to bacterial HtrA. Four human HtrAs have been identified. HtrA1 and HtrA3 share a high degree of domain organization and are downregulated in a number of cancers, suggesting a widespread loss of these proteases in cancer. This study examined how extensively the HtrA (HtrA1-3) proteins are downregulated in commonly used cancer cell lines and primary ovarian tumors. Methods. RT-PCR was applied to various cancer cell lines (n=17) derived from the ovary, en-dometrium, testes, breast, prostate, and colon, and different subtypes of primary ovarian tumors [granulosa cell tumors (n=19), mucinous cystadenocarcinomas (n=6), serous cystadenocarcino-mas (n=8)] and normal ovary (n = 9). HtrA3 protein was localized by immunohistochemistry. Results. HtrA3 was extensively downregulated in the cancer cell lines examined including the granulosa cell tumor-derived cell lines. In primary ovarian tumors, the HtrA3 was significantly lower in serous cystadenocarcinoma and granulosa cell tumors. In contrast, HtrA1 and HtrA2 were expressed in all samples with no significant differences between the control and tumors. In normal postmenopausal ovary, HtrA3 protein was localized to lutenizing stromal cells and corpus albicans. In serous cystadenocarcinoma, HtrA3 protein was absent in the papillae but detected in the mesenchymal cyst wall. Conclusion. HtrA3 is more extensively downregulated than HtrA1-2 in cancer cell lines. HtrA3, but not HtrA1 or HtrA2, was decreased in primary ovarian serous cystadenocarcinoma and granulosa cell tumors. This study provides evidence that HtrA3 may be the most relevant HtrA associated with ovarian malignancy.",
keywords = "GCT, HtrA3, Ovarian cancer, Protease, Serous cystadenocarcinoma",
author = "Harmeet Singh and Ying Li and Fuller, {Peter J.} and Craig Harrison and Jyothsna Rao and Stephens, {Andrew N.} and Gui-Ying Nie",
year = "2013",
doi = "10.7150/jca.5702",
language = "English",
volume = "4",
pages = "152--164",
journal = "Journal of Cancer",
issn = "1837-9664",
publisher = "Ivyspring International Publisher",
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}

Htra3 is downregulated in cancer cell lines and significantly reduced in primary serous and granulosa cell ovarian tumors. / Singh, Harmeet; Li, Ying; Fuller, Peter J.; Harrison, Craig; Rao, Jyothsna; Stephens, Andrew N.; Nie, Gui-Ying.

In: Journal of Cancer, Vol. 4, No. 2, 2013, p. 152-164.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Htra3 is downregulated in cancer cell lines and significantly reduced in primary serous and granulosa cell ovarian tumors

AU - Singh, Harmeet

AU - Li, Ying

AU - Fuller, Peter J.

AU - Harrison, Craig

AU - Rao, Jyothsna

AU - Stephens, Andrew N.

AU - Nie, Gui-Ying

PY - 2013

Y1 - 2013

N2 - Objective. The high temperature requirement factor A3 (HtrA3) is a serine protease homolo-gous to bacterial HtrA. Four human HtrAs have been identified. HtrA1 and HtrA3 share a high degree of domain organization and are downregulated in a number of cancers, suggesting a widespread loss of these proteases in cancer. This study examined how extensively the HtrA (HtrA1-3) proteins are downregulated in commonly used cancer cell lines and primary ovarian tumors. Methods. RT-PCR was applied to various cancer cell lines (n=17) derived from the ovary, en-dometrium, testes, breast, prostate, and colon, and different subtypes of primary ovarian tumors [granulosa cell tumors (n=19), mucinous cystadenocarcinomas (n=6), serous cystadenocarcino-mas (n=8)] and normal ovary (n = 9). HtrA3 protein was localized by immunohistochemistry. Results. HtrA3 was extensively downregulated in the cancer cell lines examined including the granulosa cell tumor-derived cell lines. In primary ovarian tumors, the HtrA3 was significantly lower in serous cystadenocarcinoma and granulosa cell tumors. In contrast, HtrA1 and HtrA2 were expressed in all samples with no significant differences between the control and tumors. In normal postmenopausal ovary, HtrA3 protein was localized to lutenizing stromal cells and corpus albicans. In serous cystadenocarcinoma, HtrA3 protein was absent in the papillae but detected in the mesenchymal cyst wall. Conclusion. HtrA3 is more extensively downregulated than HtrA1-2 in cancer cell lines. HtrA3, but not HtrA1 or HtrA2, was decreased in primary ovarian serous cystadenocarcinoma and granulosa cell tumors. This study provides evidence that HtrA3 may be the most relevant HtrA associated with ovarian malignancy.

AB - Objective. The high temperature requirement factor A3 (HtrA3) is a serine protease homolo-gous to bacterial HtrA. Four human HtrAs have been identified. HtrA1 and HtrA3 share a high degree of domain organization and are downregulated in a number of cancers, suggesting a widespread loss of these proteases in cancer. This study examined how extensively the HtrA (HtrA1-3) proteins are downregulated in commonly used cancer cell lines and primary ovarian tumors. Methods. RT-PCR was applied to various cancer cell lines (n=17) derived from the ovary, en-dometrium, testes, breast, prostate, and colon, and different subtypes of primary ovarian tumors [granulosa cell tumors (n=19), mucinous cystadenocarcinomas (n=6), serous cystadenocarcino-mas (n=8)] and normal ovary (n = 9). HtrA3 protein was localized by immunohistochemistry. Results. HtrA3 was extensively downregulated in the cancer cell lines examined including the granulosa cell tumor-derived cell lines. In primary ovarian tumors, the HtrA3 was significantly lower in serous cystadenocarcinoma and granulosa cell tumors. In contrast, HtrA1 and HtrA2 were expressed in all samples with no significant differences between the control and tumors. In normal postmenopausal ovary, HtrA3 protein was localized to lutenizing stromal cells and corpus albicans. In serous cystadenocarcinoma, HtrA3 protein was absent in the papillae but detected in the mesenchymal cyst wall. Conclusion. HtrA3 is more extensively downregulated than HtrA1-2 in cancer cell lines. HtrA3, but not HtrA1 or HtrA2, was decreased in primary ovarian serous cystadenocarcinoma and granulosa cell tumors. This study provides evidence that HtrA3 may be the most relevant HtrA associated with ovarian malignancy.

KW - GCT

KW - HtrA3

KW - Ovarian cancer

KW - Protease

KW - Serous cystadenocarcinoma

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DO - 10.7150/jca.5702

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