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[DOWNLOAD] "HRPAP20 in Ovarian Cancer and Its Regulation of AP-2 in Breast Cancer" by Jaeyong Cho * eBook PDF Kindle ePub Free

HRPAP20 in Ovarian Cancer and Its Regulation of AP-2 in Breast Cancer

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eBook details

  • Title: HRPAP20 in Ovarian Cancer and Its Regulation of AP-2 in Breast Cancer
  • Author : Jaeyong Cho
  • Release Date : January 19, 2013
  • Genre: Medical,Books,Professional & Technical,Science & Nature,
  • Pages : * pages
  • Size : 8694 KB

Description

Hormone regulated proliferation associated protein 20 (HRPAP20), a hormone regulated protein that promotes invasion, proliferation, and survival of breast cancer cells, has never been studied in ovariancancer. Therefore, we initially measured the expression of HRPAP20 in ovarian cancer cells and confirmed its protein expression in three ovarian cancer cell lines, ES-2, SKOV-3 and OVCAR-3. Recent studies suggested that estrogen regulates HRPAP20 in ERα-positive breast cancer cell lines and that expression of HRPAP20 may be associated with tamoxifen resistance. Quantitative RT-PCR was performed to measure the mRNA expression of HRPAP20 in estrogen-, tamoxifen-, combination of both-, and PRL-treated three ovarian cancer cell lines and endometrial cell line, Ishikawa. Our results showed that estrogen, tamoxifen and combination of both did not have statistically significant effect on the mRNA expression of HRPAP20 in both ovarian cancer and endometrial cell lines. However, the mRNA expression of HRPAP20 in ERβ-positive ES-2 cells showed a significant increase with PRL treatment. We speculated that PRL-PRLR interaction mediates HRPAP20 mRNA expression in ERβ-positive ES-2 cells, but this also may be the effect of cross-talk between PRL-activated signal transducer and nuclear receptor ERβ based on other established data. With respect to HRPAP20 inbreast cancer, our preliminary data showed an increase in DNA binding of transcription factor AP-2 in MCF-7 cells stably expressing HRPAP20 (MCF-7/HRPAP20 transfectants) and numerous studies suggest that AP-2α and AP-2γ play a role in tumor metastasis and cell growth in breast cancer. Therefore, we speculated that DNA binding by either AP-2α or AP-2γ is increased in MCF-7/HRPAP20 transfectants, possibly due to regulation of AP-2α or AP-2γ protein expression by HRPAP20. However, we did not observe any difference in protein expression of AP-2α and AP-2γ in MCF-7/HRPAP20 transfectants, empty vector controls and wild type MCF-7 cells. We speculated that serum may regulate the protein expression of AP-2α or AP-2γ and that the presence of serum in growth medium may interfere with our evaluation of the effect of HRPAP20 overexpression alone on AP-2α or AP-2γ protein expression. The immunoblot analysis showed that the protein expression of AP-2α was lost in absence of serum while its expression was not altered in all three cell lines with presence of serum. In addition, AP-2γ protein expression appeared to be inhibited by serum in wild type MCF-7 cells and empty vector controls while its protein expression remained same in MCF-7/HRPAP20 transfectants in presence or absence of serum. Therefore, we concluded that protein expression of AP-2α does not appear to be regulated by HRPAP20, and protein expression of both AP-2α and AP-2γ in MCF-7 may be regulated by serum by unknown mechanism. In addition, we suggest that HRPAP20 expression may suppress serum regulation of AP-2γ protein expression. We also speculated that increased DNA binding activity by AP-2 may occur by downregulating a co-repressor of AP-2s or post-transcriptional modifications. Furthermore, we suggest that it is also possible that DNA binding by other isoform of AP-2, AP-2β, AP-2δ or AP-2ε, might be the one that regulated by HRPAP20 in MCF-7/HRPAP20 transfectants.


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