Germ cell‐specific heat shock protein 70‐2 is expressed in cervical carcinoma and is involved in the growth, migration, and invasion of cervical cells

Abstract

BACKGROUND: Cervical cancer is a major cause of death among women worldwide, and the most cases are reported in the least developed countries. Recently, a study on DNA microarray gene expression analysis demonstrated the overexpression of heat shock protein 70-2 (HSP70-2) in cervical carcinoma cells (HeLa). The objective of the current study was to evaluate the association between HSP70-2 expression in cervical carcinogenesis and its potential role in various malignant properties that result in disease progression. METHODS: HSP70-2 expression was examined in various cervical cancer cell lines with different origins and in clinical cervical cancer specimens by reverse transcriptasepolymerase chain reaction (RT-PCR), flow cytometry, and immunohistochemistry (IHC) analyses. A plasmid-based, short-hairpin RNA approach was used specifically to knock down the expression of HSP70-2 in cervical tumor cells in vitro and in vivo to examine the role of HSP70-2 on various malignant properties. RESULTS: RT-PCR and IHC analyses revealed HSP70-2 expression in 86% of cervical cancer specimens. Furthermore, knockdown of HSP70-2 expression significantly reduced cellular growth, colony formation, migration, and invasion in vitro and reduced tumor growth in vivo. A significant association of HSP70-2 gene and protein expression was observed among the various tumor stages (P ¼ .046) and different grades (P ¼ .006), suggesting that HSP70-2 expression may be an indicator of disease progression. CONCLUSIONS: The current findings suggested that HSP70-2 may play an important role in disease progression in cervical carcinogenesis. Patients who had early stage disease and low-grade tumors had HSP70-2 expression, supporting its potential role in early detection and aggressive treatment modalities for cervical cancer management. Cancer 2010;116:3785-96.

ShRNA-mediated gene silencing of heat shock protein 70 inhibits human colon cancer growth

“…These results were partially supported by a recent report that HSP70 depletion eradicated hepatocellular carcinoma (17), gastric cancer (3), cervical cancer (18) and bladder carcinoma (19) in mouse xenograft models. In the current study, the results from H&E staining, anti-PCNA immunohistochemical staining and the TUNEL assay obtained from these mice were consistent with in vitro results in HT29 cell lines, indicating that HSP70 shRNA possessed growth-inhibitory and apoptosis-enhancing effects on xenograft tumors in mice.…”

HSP90 and HSP70 Proteins Are Essential for Stabilization and Activation of WASF3 Metastasis-promoting Protein

“…The association with HSP90/70 has been demonstrated clearly in this study and potentially provides a basis for other observations involving the influences of HSP70/90 over invasion. In a number of cases, involving, for example, cervical carcinoma (30) and bladder carcinoma (31), the HSP70 protein was shown to be highly expressed in advanced stage tumors suggesting a role in progression (30,31). When HSP70 was inactivated using shRNA knockdown in cell lines from cervical and bladder cancer, invasion and migration was also suppressed, in the same way these phenotypes are affected by WASF3 knockdown.…”

FOXM1 promotes tumor cell invasion and correlates with poor prognosis in early-stage cervical cancer

“…Media were supplemented with 10% fetal bovine serum (HyClone Laboratories, Logan, UT) and 1% antibiotics (100 U/ml penicillin and 100 μg/ml streptomycin) in a 5% CO 2 -humidified atmosphere at 37°C [4,25]. These five cell lines were purchased from American Type Culture Collection (ATCC, MD, USA).…”

“…In order to decrease its mortality, great efforts have been made to elucidate the molecular mechanisms responsible for cancer cell migration and invasion, and to identify tumor-specific markers for predicting cancer cell motility and invasiveness. It was recently reported that heat shock protein 70-2 [4], p38 kinase [5], glucose-regulated protein 58 [6], and EFEMP1 [7] could modulate cancer cell motility and invasiveness and could serve as prognostic markers for cervical cancer. However, there are still some limitations associated with identifying cancer cell aggressiveness, and the molecular mechanisms remain to be elucidated [3,8].…”