Biomedical subjects

Young-Mee Park

Publications and source records attributed to Young-Mee Park.

18 recordsLinked to original sources

PubMed2006

High superoxide dismutase and low glutathione peroxidase activities in red blood cells predict susceptibility of lung cancer patients to radiation pneumonitis.

Radiation pneumonitis is an unpredictable complication of radiotherapy for lung cancer and a condition which can cause significant morbidity. The ability to identify patients at a high risk of developing pneumonitis is critical, since it will enable the individualization of the treatment plan. Because the cytotoxic effect of radiation is propagated through reactive oxygen species (ROS) and ROS-driven oxidative stress, the role of antioxidant defense systems in radiation pneumonitis was investigated. Using the pneumonitis-sensitive C3H/HeN mice as a model, we demonstrated that the antioxidant response of the lung correlated well with that of red blood cells (RBC). We then proceeded to test whether differences of RBC antioxidant response would predict the pneumonitis development in patients. Superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) activities and glutathione in RBC were measured at baseline and then weekly for 6 weeks of treatment in 15 eligible patients receiving concurrent chemo-radiotherapy for unresectable stage III NSCLC. Striking differences were found in the antioxidant activities of RBC with respect to the pneumonitis development. Those who developed pneumonitis showed higher SOD and lower GPX activities at baseline compared to those who did not (3.7 vs 6.8 units/mg for median SOD, 16.5 vs 10.7 nmol/min/mg for median GPX). The functional imbalance of SOD and GPX was displayed consistently throughout the treatment period. The sensitivity and specificity of pneumonitis prediction were further increased when the GPX/SOD ratio was analyzed (pretreatment P = 0.0046). Our results provide a strong rationale to monitor SOD and GPX activities of RBC to identify patients who are at risk of developing pneumonitis, and to implement a strategy of increasing the GPX/SOD ratio in order to lower the risk.

Adult↗

PubMed2006

Prx1 suppresses radiation-induced c-Jun NH2-terminal kinase signaling in lung cancer cells through interaction with the glutathione S-transferase Pi/c-Jun NH2-terminal kinase complex.

Radiotherapy is one of the major treatment modalities for lung cancer. Cell killing by ionizing radiation is mediated primarily through the reactive oxygen species (ROS) and ROS-driven oxidative stress. Prx1, a peroxiredoxin family member, was shown to be frequently elevated in lung cancer cells and tissues. Although the antioxidant function of Prx1 is expected to affect the radiotherapy response of lung cancer, the physiologic significance of its peroxidase activity in irradiated cells is unclear because the catalytic Cys52 is easily inactivated by ROS due to its overoxidation to sulfinic or sulfonic acid. In this study, we investigated the role of Prx1 in radiation sensitivity of human lung cancer cells, with special emphasis on the redox status of the catalytic Cys52. We found that overexpression of Prx1 enhances the clonogenic survival of irradiated cells and suppresses ionizing radiation-induced c-Jun NH2-terminal kinase (JNK) activation and apoptosis. The peroxidase activity of Prx1, however, is not essential for inhibiting JNK activation. The latter effect is mediated through its association with the glutathione S-transferase pi (GSTpi)-JNK complex, thereby preventing JNK release from the complex. Reduced JNK activation is observed when the peroxidase activity of Prx1 is compromised by Cys52 overoxidation or in the presence of the Cys52 to Ser52 mutant (Prx1C52S) lacking peroxidase activity. We show that both Prx1 and Prx1C52S interact with the GSTpi-JNK complex and suppress the release of JNK from the complex. Our study provides new insight into the antiapoptotic function of Prx1 in modulating radiosensitivity and provides the impetus to monitor the influence of Prx1 levels in the management of lung cancer.

Antioxidants↗

PubMed2006

Hypoxia increases androgen receptor activity in prostate cancer cells.

Recent studies show that prostate cancer cells are able to survive in a hypoxic tumor environment, and the extent of tumor hypoxia correlates with poor clinical outcome. Androgen deprivation, the most common form of prostate cancer therapy, was itself shown to induce a state of transient hypoxia at the microenvironmental level. Because androgen receptor (AR) signaling plays a critical role in prostate cancer, we investigated the effect of hypoxia in regulating AR function. We found that in LNCaP prostate cancer cells, AR binding to the androgen-responsive element (ARE), prostate-specific antigen accumulation, and ARE-reporter gene activity were increased after hypoxia treatment. Hypoxia-enhanced AR function was also observed when AR was exogenously introduced into AR-null DU145 cells. Confocal microscopy and chromatin immunoprecipitation assays showed that AR translocation to the nucleus and AR recruitment to the prostate-specific antigen promoter were facilitated after hypoxia treatment. The AR stimulatory effect seemed to be ligand-dependent because it was abrogated when cells were cultured in an androgen-depleted medium, but was restored with the addition of R1881, a synthetic androgen. The sensitivity of AR activation to R1881 was also increased after hypoxia treatment. Although concentrations of <1 nmol/L R1881 did not induce ARE reporter activity under normoxic conditions, exposure to hypoxia greatly potentiated the AR response to low levels of R1881. Collectively, our results provide compelling evidence that changes in hypoxia/reoxygenation stimulate AR trans-activation and sensitization. The AR-stimulatory effect of an unstable tissue oxygenation milieu of a tumor is likely to contribute to treatment resistance and the emergence of recurrent prostate cancer.

Cell Hypoxia↗

PubMed2006

Analysis of human plasma proteome by 2DE- and 2D nanoLC-based mass spectrometry.

We compared the 2DE coupled to MALDI-TOF-MS and ESI-MS/MS analysis (2DE-MS) and the on-line 2D nanoLC, followed by nanoESI-MS/MS analysis (2DLC-MS), for the separation and identification of proteins in high abundance protein-depleted human plasma. Identification of proteins in the plasma by the two methods demonstrated that the majority of the identified protein set was unique to each method. Therefore, if a comprehensive coverage of the proteome identification is desired, it is ideal to apply both methods. The 2DE-MS method is amenable to protein spot-based quantitation, whereas the 2DLC-MS method may provide an advantage of the high throughput application.

Adult↗

PubMed2006

Effect of ionizing radiation on rat tissue: proteomic and biochemical analysis.

Reactive oxygen species (ROS), generated by ionizing radiation, has been implicated in its effect on living tissues. We confirmed the changes in the oxidative stress markers upon irradiation. We characterized the changes in the proteome profile in rat liver after administering irradiation, and the affected proteins were identified by MALDI-TOF-MS and ESI-MS/MS. The identified proteins represent diverse sets of proteins participating in the cellular metabolism. Our results demonstrated that proteomics analysis is a useful method for characterization of a global proteome change caused by ionizing radiation to unravel the molecular mechanisms involved in the cellular responses to ionizing radiation.

Animals↗

PubMed2006

Neural network-based analysis of thiol proteomics data in identifying potential selenium targets.

Generation of a monomethylated selenium metabolite is critical for the anticancer activity of selenium. Because of its strong nucleophilicity, the metabolite can react directly with protein thiols to cause redox modification. Here, we report a neural network-based analysis to identify potential selenium targets. A reactive thiol specific reagent, BIAM, was used to monitor thiol proteome changes on 2D gel. We constructed a dynamic model and evaluated the relative importance of proteins mediating the cellular responses to selenium. Information from this study will provide new clues to unravel mechanisms of anticancer action of selenium. High impact selenium targets could also serve as biomarkers to gauge the efficacy of selenium chemoprevention.

Antineoplastic Agents↗

PubMed2006

Analysis of protein redox modification by hypoxia.

We examined hypoxia-induced changes in global thiol proteome profile in human prostate cancer cells using a BIAM-based display method. We analyzed the kinetics of protein thiol modification by using a pattern recognition algorithm, self-organizing maps (SOM) clustering, and identified the BIAM-labeled proteins by MALDI-TOF and ESI-tandem mass spectrometry. We found 99 out of 215 of total BIAM-labeled proteins were affected by hypoxia treatment and, yet, with diverse patterns and kinetics of redox modification. Our study proved that proteomics analysis employing the BIAM-labeling method can provide valuable information pertaining to global changes in the redox status of proteins in response to hypoxia.

Apoptosis↗

PubMed2006

Differential expression of Bcl-2, Bcl-XL and p53 in colorectal cancer.

AIMS: The balance between proliferation and apoptosis is often disturbed in cancer. The aim of this study was to investigate the possible role of Bcl-2 gene family members and p53 as prognostic factors in a series of colorectal cancer. METHODS: The immunohistochemical expression of Bcl-2 gene family members (Bcl-2 and Bcl-X(L)) and p53 was evaluated in 81 surgical specimens of primary human colorectal cancers to establish the role of these genes in colorectal cancer and to evaluate their prognostic importance. RESULTS: The expression of Bcl-2 correlated with early clinical stage and lack of lymphovascular invasion and lymph node involvement. The expression of p53 correlated with less differentiated status and with perineural invasion. p53 expression showed negative correlation with Bcl-X(L) expression (P = 0.025) and no correlation with Bcl-2 expression. CONCLUSIONS: p53 expression may be a less favorable marker and Bcl-2 expression a more favorable marker of behavior. Bcl-2 and Bcl-X(L) may play an independent role in disease progression, and the expression of these proteins may be under independent regulatory control in colorectal cancer.

Biomarkers, Tumor↗

PubMed2005

Endoplasmic reticulum stress signal mediators are targets of selenium action.

A monomethylated selenium metabolite, called methylseleninic acid (MSA), has recently been shown to cause global thiol redox modification of proteins. These changes represent a form of cellular stress due to protein misfolding or unfolding. An accumulation of aberrantly folded proteins in the endoplasmic reticulum (ER) triggers a defined set of transducers to correct the defects or commit the cells to apoptosis if the rescue effort is exhausted. Treatment of PC-3 human prostate cancer cells with MSA was found to induce a number of signature ER stress markers: (a) the survival/rescue molecules such as phosphorylated protein kinase-like ER-resident kinase (phospho-PERK), phosphorylated eukaryotic initiation factor-2alpha (phospho-eIF2alpha), glucose-regulated protein (GRP)-78, and GRP94; and (b) the apoptotic molecules such as caspase-12, caspase-7, and CAAT/enhancer binding protein homologous protein or growth arrest DNA damage-inducible gene 153 (CHOP/GADD153). Additional evidence suggested that CHOP/GADD153 might be an important transcription factor in apoptosis induction by MSA. In general, a higher concentration of MSA was required to elicit the apoptotic markers compared with the rescue markers. The apoptotic markers increased proportionally with the dose of MSA, whereas the rescue markers failed to keep pace with the increasing challenge from MSA. GRP78 is the rheostat of the ER stress transducers. In GRP78-overexpressing cells, the ability of MSA to up-regulate phospho-PERK, phospho-eIF2alpha, GRP94, caspase-12, caspase-7, and CHOP/GADD153 was significantly muted. A generous supply of GRP78 would allow cells to cope better with ER stress, thereby improving the odds for survival and negating the commitment to apoptotic death. The present study thus provides strong evidence to support an important role of ER stress response in mediating the anticancer effect of selenium.

Apoptosis↗

PubMed2005

Slc7a11 gene controls production of pheomelanin pigment and proliferation of cultured cells.

In mammals, >100 genes regulate pigmentation by means of a wide variety of developmental, cellular, and enzymatic mechanisms. Nevertheless, genes that directly regulate pheomelanin production have not been described. Here, we demonstrate that the subtle gray (sut) mouse pigmentation mutant arose by means of a mutation in the Slc7a11 gene, encoding the plasma membrane cystine/glutamate exchanger xCT [Kanai, Y. & Endou, H. (2001) Curr. Drug Metab. 2, 339-354]. A resulting low rate of extracellular cystine transport into sut melanocytes reduces pheomelanin production. We show that Slc7a11 is a major genetic regulator of pheomelanin pigment in hair and melanocytes, with minimal or no effects on eumelanin. Furthermore, transport of cystine by xCT is critical for normal proliferation, glutathione production, and protection from oxidative stress in cultured cells. Thus, we have found that the Slc7a11 gene controls the production of pheomelanin pigment directly. Cells from sut mice provide a model for oxidative stress-related diseases and their therapies.

Amino Acid Transport System y+↗

PubMed2004

Association between polymorphisms of ERCC1 and XPD and survival in non-small-cell lung cancer patients treated with cisplatin combination chemotherapy.

ERCC1 (excision repair cross-complementation group 1) and XPD (ERCC2, excision repair cross-complementation group 2) as genes have been known to be belonged to the nucleotide excision repair pathway and therefore related to DNA repair. Polymorphisms in these genes have been rarely evaluated in terms of predicting cancer patient survival. We investigated whether these polymorphisms have an effect on response to chemotherapy and survival in 109 patients with non-small-cell lung cancer treated with cisplatin combination chemotherapy. Polymorphisms of ERCC1 Asn118Asn (C --> T), XPD Lys751Gln (A --> C) and Asp312Asn (G --> A) were evaluated using a SNaPshot kit. As for chemotherapy response, treatment response did not show statistically significant differences between the wild genotypes and the variant genotypes for the ERCC1 and XPD gene. The median survival time of all patients was 376 days (95% CI, 291-488). As for survival rate according to the polymorphism of codon 118 in ERCC1, median survival time in patients showing C/C genotype was 486 days (95% CI, 333-x), which was significantly different from the 281 days (95% CI, 214-376) of patients with the variant genotype (T/T or C/T) (P = 0.0058). Using the Cox-proportional hazards model, the polymorphism of codon 118 in ERCC1, response to chemotherapy, weight loss and performance status effected overall survival significantly (P = 0.0001, 0.0001, 0.0028 and 0.0184, respectively). However, polymorphisms of codons 751 and 312 in the XPD gene did not affect patient survival (P = 0.4711 and 0.4542, respectively). Therefore, we suggest that the C/C genotype in codon 118 of ERCC1 is a surrogate marker for predicting better survival in non-small-cell lung cancer patients treated with cisplatin combination chemotherapy.

Adult↗

PubMed2003

Cloning and characterization of the rat Hsf2 promoter: a critical role of proximal E-box element and USF protein in Hsf2 regulation in different compartments of the brain.

The complex patterns of tissue-, cell type- and developmental stage-specific expression of heat shock factor 2 (Hsf2) raise a question of how this can be achieved for this ubiquitous transcription factor. To explore molecular mechanisms responsible for the regulated expression of Hsf2, a 2638-bp 5'-flanking region of the rat Hsf2 gene was cloned and characterized. Since the brain represents one of the most complicated organs composed of several regions with different cell types, differential regulation of Hsf2 in various brain regions was investigated in detail. Results show that the major transcription initiation site of the Hsf2 gene is located at cytosine-155 relative to the translation initiation site. The E-box element located immediate upstream of the transcription initiation site was demonstrated to be critical for Hsf2 promoter activity, and the upstream stimulatory factor (USF) protein was identified as the major E-box binding protein. That the only two base exchange of the E-box core sequences from CACGTG to CACGGT severely impaired Hsf2 promoter activity and completely eliminated USF binding clearly demonstrated that the specific binding of USF to E-box is critical for Hsf2 promoter activity. Here we demonstrated that the Hsf2 expression levels varied significantly in different brain regions. We also demonstrated that Hsf2 expression levels in various brain regions relatively correlated with the E-box binding activity of USF. Based on these results, we suggest that E-box binding activity of USF protein may act as one of the major regulators of Hsf2 expression in situ although a possible involvement of other transcription factors cannot be ruled out. The presence of several transcription factor binding sites of biological importance in the Hsf2 promoter suggests that identifying the interplay of USF and these factors should help further elucidate the molecular mechanisms of tissue-, cell type- and developmental stage-specific expression of Hsf2.

5' Flanking Region↗

PubMed2003

Identification of estrogen-regulated genes in the mouse uterus using a delayed-implantation model.

Gonadal steroid hormones are known to modulate the implantation of the blastocyst, but how the controlling genetics are regulated remains largely unknown. Using a delayed-implantation model, we examined estrogen-regulated genes (ERGs) in the mouse uterus using the differential-display reverse transcription-polymerase chain reaction (DD RT-PCR). Pregnant mice were ovariectomized and injected daily with progesterone (P, 1 mg/mouse), followed by a single injection of estrogen (E, 200 ng/mouse); 24 or 48 hr later, total RNA was extracted from the uterus. Reverse Northern analysis verified the expression patterns of 36 clones out of thousands of RNA species. Only five clones had mRNA levels that were modified, whereas other mRNAs were unchanged or not detectable. Sequence analysis of these, using the Basic Local Alignment Search Tool (BLAST) service, revealed that four of these clones were novel; one clone, designated ERG10, was found to be the mouse homologue of that deleted in oral cancer DOC-1. DOC-1 mRNA was detected all tissues examined, but only in the uterus and cervix was markedly increased 12 hr after E administration, it returned to basal level by 48 hr. One of the novel genes, designated ERG8, had three different forms of mRNAs and was expressed ubiquitously in all examined tissues. In the uterus, the mRNA level of ERG8 also increased 12 hr after E administration. These results suggest that during the implantation process, E differentially regulates several genes depending on cell type. Uterine-specific induction of newly found genes, such as ERG8 and 10, by E appears to be important for the early implantation process.

Animals↗

PubMed2003

Differential, stage-dependent expression of Hsp70, Hsp110 and Bcl-2 in colorectal cancer.

BACKGROUND: The presence of hypoxic cells in solid tumors has been suggested to contribute to the malignant progression of various tumors. Recently, we reported an activation of heat shock transcription factor (HSF) and expression of heat shock proteins (Hsp) in murine tumor cells by hypoxia. METHODS: To search for a possible role of Hsp in the malignant progression of human tumors, we analyzed the expression profiles of Hsp family proteins in weakly and highly metastatic human colorectal cancer (CRC) cell lines. We also analyzed the expression profiles of Bcl-2 family proteins because the altered expression of these proteins has been demonstrated in various solid tumors. RESULTS: In the present paper we showed among various Hsp and Bcl-2 family proteins that the expression of Hsp70 and Hsp110 was elevated in highly metastatic CX-1 and HT-29 cells, while the expression of Bcl-2 was elevated in weakly metastatic MIP-101 and Clone A cells. Subsequent immunohistochemical analysis of 81 primary human CRC tissues demonstrated that the expression of Hsp70 and Hsp110 was highly correlated with the advanced clinical stages and positive lymph node involvement. The expression of Bcl-2, in contrast, was correlated to the early clinical stage and negative lymphovascular invasion. CONCLUSION: Taken together, our study demonstrated for the first time a differential, stage-dependent expression of Hsp70, Hsp110 and Bcl-2 in CRC. We suggest that the molecular mechanisms underlying the differential expression of Hsp and Bcl-2 family members deserves a more rigorous future study, the results of which might offer novel modes of rationale and strategy to predict and manipulate the malignant progression of colorectal cancers.

Biomarkers, Tumor↗

PubMed2002

Differential expression of Prx I and II in mouse testis and their up-regulation by radiation.

Testis is one of the most sensitive organs to ionizing radiation. The present study was designed to unravel the possible role of antioxidant proteins, peroxiredoxin I and II (Prx I and II) in the testis. Our results show that Prx I and II are constitutively expressed in the testis and their expression levels are decreased to some extent as the testis develops. Interestingly, immunohistochemical analysis revealed a preferential expression of Prx I and II in Leydig and Sertoli cells, respectively. Neither Prx I nor Prx II expression was obvious in the testicular germ cells including spermatogonia and spermatocytes. Ionizing radiation exerted oxidative stress on the testis and induced apoptosis primarily in the germ cells. When the irradiated testis was examined, the Prx system was found to be transiently up-regulated. Taken together, we suggest that the relative radiation-resistance of Leydig and Sertoli cells could be attributed in part to the antioxidant function of the Prx system in these cells.

Animals↗

PubMed2002

Activation of dynamin I gene expression by Sp1 and Sp3 is required for neuronal differentiation of N1E-115 cells.

Dynamin I is a key molecule required for the recycling of synaptic vesicles in neurons, and it has been known that dynamin I gene expression is induced during neuronal differentiation. Our previous studies established that neuronal restriction of dynamin I gene expression is controlled by Sp1 and nuclear factor-kappaB-like element-1. Here, using a series of deletion constructs and site-directed mutation, we found that transcription of dynamin I gene during neuronal differentiation of N1E-115 cells is controlled primarily by the Sp1 element located between -13 to -4 bp of the dynamin I promoter. Gel shift analysis demonstrated that in addition to Sp1, Sp3 could interact with this Sp1 element. The requirement for Sp family transcription factors in dynamin I gene expression was confirmed by using mithramycin, an inhibitor of Sp1/Sp3 binding. Mithramycin repressed dynamin I gene expression and resulted in blocking of neuronal differentiation of N1E-115 cells. The localization of the dynamin I protein was also restricted in the peripheral region of the nucleus by the mithramycin treatment. Thus, all of our results suggest that induction of dynamin I gene expression during N1E-115 cell differentiation is modulated by Sp1/Sp3 interactions with the dynamin I promoter, and its expression is important for neuronal differentiation of the N1E-115 cells.

Animals↗

PubMed2002

Expression pattern of HSP25 in mouse preimplantation embryo: heat shock responses during oocyte maturation.

Heat shock proteins (HSPs) are known to play an important role not only in various stress conditions such as exposure to heat shock, but also in normal development and/or differentiation. The role of small heat shock proteins such as HSP25 in early embryo development remains largely unknown. In the present study, we examined temporal and spatial expression patterns of HSP25 during mouse preimplantation embryo development. Reverse transcription-polymerase chain reaction (RT-PCR) showed that hsp25 mRNA was detected in unfertilized eggs. Hsp25 mRNA was induced by zygotic gene activation at 2-cell stage, decreased slightly at 4-cell, and re-increased at morula, with the highest level at blastocyst stage. Interestingly, another form of hsp25 variant of which 156 bp (52 a.a.) was truncated within the exon1 region was observed in all stages of preimplantation embryos. We also investigated the sub-cellular localization of HSP25 by fluorescence immunocytochemistry. HSP25 was detected in the cytoplasm under normal developmental condition. While acute heat shock (at 43 degrees C for 30 min) caused no significant changes in the sub-cellular localization of HSP25 in the developing mouse embryos, chronic heat shock (at 43 degrees C for 3 hr) resulted in a denser immunostaining of HSP25 in the nucleus than in the cytoplasm, indicating a nuclear translocation of HSP25 by heat shock. As hsp25 mRNA was detected in the unfertilized egg as a maternal transcript, we examined the expression of hsp25 mRNA with RT-PCR during oocyte maturation under normal and heat shock conditions. Hsp25 mRNA was detected at GV (germinal vesicle)-, GVBD (germinal vesicle breakdown)-, and MII (metaphase II)-oocytes. The expression of hsp25 mRNA was increased markedly by both acute (for 30 min and 1 hr) and chronic (for 4 hr) heat shock, but returned to the basal level during recovery from heat shock in a time-dependent manner, suggesting a thermo-protective role of HSP25. In contrast to preimplantation embryos, HSP25 was detected both in the cytoplasm and the nucleus except for the nucleolus, and the cellular localization was not altered by heat shock. Finally, we investigated the effect of heat shock on oocyte maturation. When GV-oocytes were exposed to acute heat shock (at 43 degrees C for 15 min to 1 hr), they underwent the GVBD and the PB (polar body) emission successfully. However, under more stringent heat shock conditions (at 43 degrees C for 2-4 hr), most oocytes were arrested at the GV-stage, and the first PB was not developed, indicating that chronic heat shock might be inhibitory to the mouse oocyte maturation. Taken together, these findings suggest that HSP25 is important for mouse preimplantation embryo development and oocyte maturation.

Animals↗

PubMed2002

Induction of adaptive response by low-dose radiation in RIF cells transfected with Hspb1 (Hsp25) or inducible Hspa (Hsp70).

An adaptive response results in a reduced effect of a high challenging dose of a stressor after a smaller, inducing dose has been applied a few hours earlier. Radiation-induced fibrosarcoma (RIF) cells did not show an adaptive response, i.e. a reduced effect from a high challenging dose (2 Gy) of a radiation after a priming dose (1 cGy) had been applied 4 or 7 h earlier, but cells of a thermoresistant clone (TR) derived from RIF cells did. Since the expression of inducible Hspa (also known as Hsp70) and Hspb1 (also known as Hsp25) was different in these two cell lines, the role of inducible Hspa and Hspb1 in the adaptive response was examined. When RIF cells were transfected with inducible Hspa or Hspb1, both radioresistance measured by clonogenic assays and a reduction of apoptosis were detected. The adaptive response was also acquired by these two cell lines. The inducible Hspa transfectant showed a more pronounced adaptive response than the Hspb1 transfectant. Based on these results, it appears that inducible Hspa and Hspb1 are at least partly responsible for the induction of the adaptive response in these cells. Moreover, when inducible Hspa or Hspb1 was transfected into RIF cells, co-regulation of the two genes was detected. Heat-shock factor (Hsf) was found to be at least partially responsible for the induction of the adaptive response in these cells.

Adaptation, Physiological↗